www.PCOSTreatmentReport.com
https://www.mcgill.ca/newsroom/channels/news/polycystic-ovary-syndrome-increases-risk-gestational-diabetes-and-hypertensive-disorders-325178
Polycystic ovary syndrome increases risk for gestational diabetes and hypertensive disorders
News
McGill researchers make gains in understanding pregnancy-associated metabolic complications
https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-020-00701-z
https://www.ncbi.nlm.nih.gov/pubmed/32921318?dopt=Abstract
Troxerutin protects against DHT-induced polycystic ovary syndrome in rats.
J Ovarian Res. 2020 Sep 13;13(1):106
Authors: Gao Z, Ma X, Liu J, Ge Y, Wang L, Fu P, Liu Z, Yao R, Yan X
Abstract
The exact pathogenesis of polycystic ovary syndrome (PCOS), the most common neuroendocrine disorder in women of reproductive age, has not been fully elucidated. Recent studies suggested that chronic inflammation and neurotransmitter disorder involved in the progress of PCOS. Troxerutin, a natural flavonoid, was reported to possess neuroprotective effect in several disease models by inhibiting inflammation or enhancing neurotrophic factor. In this study, we investigated the possible protective effect and mechanism of troxerutin in a dihydrotestosterone (DHT)-induced rat model of PCOS. The PCOS rat models were treated with troxerutin at a dose of 150 mg/kg or 300 mg/kg for up to 4 weeks. Results showed that 300 mg/kg troxerutin significantly decreased the body weight gain and improved the pathological changes of ovary induced by DHT. Meanwhile, the elevated gonadotrophin-releasing hormone (GnRH), gonadotrophin and testosterone in the serum of PCOS rats were reduced with the treatment of troxerutin. The expression of kisspeptin and NKB in arcuate nucleus and their receptors kiss1r and NK3r in GnRH positive neurons of median eminence were markedly decreased in troxerutin-treated rats. Of note, the GnRH inhibitory regulator GABA and stimulatory regulator glutamate were also restored to the normal level by troxerutin. The present study indicated that troxerutin may exhibit a protective effect in PCOS rat model via regulating neurotransmitter release.
PMID: 32921318 [PubMed – in process]
https://journals.lww.com/acsm-msse/Abstract/9000/Interrupting_Prolonged_Sitting_and_Endothelial.96186.aspx
https://www.ncbi.nlm.nih.gov/pubmed/32925494?dopt=Abstract
Interrupting Prolonged Sitting and Endothelial Function in Polycystic Ovary Syndrome.
Med Sci Sports Exerc. 2020 Sep 11;:
Authors: Taylor FC, Dunstan DW, Fletcher E, Townsend MK, Larsen RN, Rickards K, Maniar N, Buman M, Dempsey PC, Joham AE, Cohen N, Owen N, Moran LJ, Green DJ
Abstract
PURPOSE: In healthy adults, the impairment of vascular function associated with prolonged sitting can be mitigated with intermittent brief bouts of activity. It is unknown whether these benefits extend to women with polycystic ovary syndrome (PCOS), in whom vascular function is typically impaired and sitting time is high. We examined the acute impact of regularly interrupting sitting time with brief simple resistance activities (SRAs) on vascular function in PCOS.
METHODS: In a randomized crossover trial, 13 physically inactive women with PCOS (18-45 years) completed two 3.5h conditions: 1) uninterrupted sitting (SIT) and 2) sitting interrupted by 3-min bouts of SRAs every 30 min. Femoral artery flow-mediated dilation (FMD), resting shear rate and resting blood flow were measured at 0h, 1h and 3.5h.
RESULTS: Mean resting femoral shear rate, averaged across the 3.5h, significantly increased in the SRA condition relative to the SIT condition (40.1 ± 6.1/s vs 62.8 ± 6.1/s, P < 0.0001). In addition, mean resting blood flow also significantly increased across the 3.5h for SRA relative to SIT (45.0 ± 9.8 ml/min vs 72.8 ± 9.9 ml/min, P < 0.0001). There were no differences between conditions in the temporal change in femoral artery FMD across 3.5h (Ptime x condition > 0.05 for all).
CONCLUSION: Frequently interrupting sitting with SRAs acutely increased resting shear rate and blood flow in women with PCOS, but did not alter FMD. With sedentary behavior increasing in prevalence, longer term studies of similar interventions to reduce and break up sitting time are warranted.
PMID: 32925494 [PubMed – as supplied by publisher]
https://www.refinery29.com/en-gb/2020/09/10005395/polycystic-ovary-syndrome-and-psychiatric-disorders
Polycystic Ovary Syndrome Fuelled My Eating Disorder
https://clinicaltrials.gov/ct2/show/NCT02653911?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=08%2F26%2F2020&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Other: Acupuncture; Other: Sham-acupuncture group
Sponsor : Guang’anmen Hospital of China Academy of Chinese Medical Sciences
Not yet recruiting
Electroacupuncture on Menstrual Frequency in Women With Polycystic Ovary Syndrome: Study Protocol
NCT02653911
Wed, 13 Jan 2016 12:00:00 EST
Last Update Posted: 09/09/20 08:16AM
https://www.frontiersin.org/articles/10.3389/fendo.2020.00621/full
https://www.ncbi.nlm.nih.gov/pubmed/33013699?dopt=Abstract
Causal Effects of Genetically Determined Metabolites on Risk of Polycystic Ovary Syndrome: A Mendelian Randomization Study.
Front Endocrinol (Lausanne). 2020;11:621
Authors: Sun S, Jiao M, Han C, Zhang Q, Shi W, Shi J, Li X
Abstract
Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that is influenced by both genetic and environmental factors. However, the etiology of PCOS remains unclear. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of genetically determined metabolites (GDMs) on the risk of PCOS. We used summary level data of a genome-wide association study (GWAS) on 486 metabolites (n = 7,824) as exposure and a PCOS GWAS consisting of 4,138 cases and 20,129 controls as the outcome. Both datasets were obtained from publicly published databases. For each metabolite, a genetic instrumental variable was generated to assess the relationship between the metabolite and PCOS. For MR analysis, we primarily used the standard inverse variance weighted (IVW) method, while three additional methods-the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods-were performed as sensitivity analyses. Results: Using genetic variants as predictors, we observed a robust relationship between epiandrosterone sulfate (EPIA-S) and PCOS (P IVW = 0.0186, P MR-Egger = 0.0111; P Weighted-median = 0.0154, and P MR-PRESSO = 0.0290). Similarly, 3-dehydrocarnitine, 4-hydroxyhippurate, hexadecanedioate, and β-hydroxyisovalerate may also have causal effects on PCOS development. Conclusions: We identified metabolites that might have causal effects on PCOS development. Our study emphasizes the role of genetic factors underlying the causal relationships between metabolites and PCOS and provides novel insights through the integration of metabolomics and genomics to better understand the mechanisms involved in human disease pathogenesis.
PMID: 33013699 [PubMed – in process]
https://www.hindawi.com/journals/ije/2020/1380176/
https://www.ncbi.nlm.nih.gov/pubmed/32934654?dopt=Abstract
Related Articles
Pentraxin 3 Levels in Young Women with and without Polycystic Ovary Syndrome (PCOS) in relation to the Nutritional Status and Systemic Inflammation.
Int J Endocrinol. 2020;2020:1380176
Authors: Wyskida K, Franik G, Choręza P, Pohl N, Markuszewski L, Owczarek A, Madej P, Chudek J, Olszanecka-Glinianowicz M
Abstract
Objective: The aim of the study was to assess PTX3 levels in PCOS and non-PCOS women in relation to nutritional status and circulating markers of inflammation.
Methods: The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight, and 61 obese) and 61 non-PCOS women (24 normal weight, 19 overweight, and 18 obese). Body composition was assessed by bioimpedance, and plasma levels of pentraxin 3 (PTX3), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP-1) were measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was made.
Results: Plasma PTX3, TNF-α, and IL-6 levels and HOMA-IR were higher in PCOS than in non-PCOS group (p < 0.001). There were positive correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) and free androgen index but negative between log10 (estradiol) levels in PCOS. While in the non-PCOS group, the correlations between log10 (PTX3) and log10 (BMI), waist circumference and fat percentage, as well as log10 (HOMA-IR) were negative. The positive correlations between PTX3 and MPC-1 and log10 (IL-6) were shown in the PCOS group only. In multivariate regression analyses, variability in PTX3 levels in the PCOS group was proportional to log10 (BMI), waist circumference, and fat percentage, but inversely proportional to log10 (estradiol) levels. While in the non-PCOS group, PTX3 levels were inversely proportional to all anthropometric parameters. Conclusions: Our results show that the decrease in PTX3 levels observed in obese is distorted in PCOS by microinflammation, and possibly, dysfunction of stroma adipose tissue and liver steatosis is reflected by enhanced insulin resistance. PMID: 32934654 [PubMed]
Anti-Mullerian Hormone Predicted PCOS, Correlated with PCOM in Women With Acne
Anti-Mullerian Hormone Predicted PCOS, Correlated with PCOM in Women With Acne
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457150/
https://www.ncbi.nlm.nih.gov/pubmed/32923927?dopt=Abstract
Matrix metalloproteinase-9 increases and Interleukin-10 reduces with increase in body mass index in polycystic ovary syndrome: A cross-sectional study.
Int J Reprod Biomed. 2020 Aug;18(8):605-610
Authors: Sylus AM, Nandeesha H, Chitra T
Abstract
Background: Obesity, inflammation and alterations in matrix metalloproteinase-9 (MMP-9) and nitric oxide (NO) levels are involved in the development of polycystic ovary syndrome (PCOS).
Objective: To investigate the relationship of MMP-9, NO and interleukin-10 (IL-10) with the increase in body mass index (BMI) in women with PCOS.
Materials and Methods: Sixty two infertile PCOS women were included in the study. Serum levels of NO, IL-10 and MMP-9 were assessed in the women with increase in BMI.
Results: MMP-9 was significantly increased (p = 0.029) and IL-10 (p = 0.015) was significantly reduced in obese PCOS subjects compared to those with lesser BMI. MMP-9 levels positively correlated with the duration of infertility (r = 0.253, p = 0.047) and negatively correlated with NO levels (r = – 0.259, p = 0.042). A significant negative correlation between the interleukin-10 levels and the BMI (r = – 0.272, p = 0.033) was also found in the PCOS subjects.
Conclusion: MMP-9 levels are increased in obese PCOS women and it is associated with NO levels and the duration of infertility.
PMID: 32923927 [PubMed]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476111/
https://www.ncbi.nlm.nih.gov/pubmed/32913539?dopt=Abstract
Effect of rNA interference on Oatp3a1 gene expression on biological characteristics and immune factors of ovarian granulosa cells in rats with PCOS.
Am J Transl Res. 2020;12(8):4659-4668
Authors: Yi W, Li X, Chen K, Li J, Chen K, Pan A
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrinal metabolic disease, and its pathogenesis has not yet been thoroughly studied. The purpose of this experiment was to investigate the effect of RNA interference on Oatp3a1 gene expression on the biological viability and immune factors of ovarian granulosa cells in rats with PCOS. First, rats were intragastrically administered 1 mg/kg letrozole to successfully construct PCOS model. Western blot, qRT-PCR, CCK8 and flow cytometry were used to detect the gene expression, immune factor protein expression, cell proliferation and apoptosis in ovarian granulosa cells transfected with siRNA Oatp3a1 in rats with PCOS, respectively. The results showed that follicle stimulating hormone receptor (FSHR) was located on the cell membrane of rat ovarian granulosa cells, and letrozole successfully induced PCOS rat model. In PCOS rat ovarian granulosa cells, the mRNA expression level of Oapta1 was higher than that in normal rat ovarian granulosa cells. At the same time, compared with the sham group, the protein expression of NF-κB, TGF-β1 and VEGF in si-Oatp3a1 group was significantly down-regulated (P < 0.05), and the cell proliferation rate was significantly decreased in si-Oatp3a1 group (P < 0.05) in comparison with the sham group. The apoptotic rate was increased obviously (P < 0.05), which was about 2.5 times that of the sham group. This indicates that in the ovarian granulosa cells of rats with PCOS, the interference of Oatp3a1 gene expression can significantly inhibit cell proliferation and promote apoptosis, while inhibiting the expression of immune factors TGF-β1 and VEGF can reduce the expression of NF-κB protein, thereby suppressing the activation of the NF-κB signaling pathway. PMID: 32913539 [PubMed]
https://nutritionj.biomedcentral.com/articles/10.1186/s12937-020-00601-4
https://www.ncbi.nlm.nih.gov/pubmed/32782010?dopt=Abstract
Related Articles
The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial.
Nutr J. 2020 Aug 11;19(1):82
Authors: Tabrizi FPF, Farhangi MA, Vaezi M, Hemmati S
Abstract
BACKGROUND: There is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS).
METHODS: In a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention.
RESULTS: After the 12-week intervention, there were significant decreases in weight (- 6.97 ± 0.52 vs. -3.19 ± 0.72 kg; P < 0.001), waist circumference (- 7.78 ± 2.50 vs. -3.73 ± 1.40 cm; P < 0.001), fat mass (- 5.19 ± 0.53 vs. -1.36 ± 0.39 kg; P < 0.001), and insulin levels (- 5.40 ± 1.86 vs. -1.19 ± 0.85 μU/mL; P < 0.001) in the spinach-derived thylakoid group compared to the placebo group. Furthermore, insulin resistance markers and serum levels of testosterone decreased significantly in the thylakoid group compared to the placebo group (P < 0.05). The changes in other parameters did not show significant differences between the two groups. CONCLUSIONS: Spinach-derived thylakoid supplementation resulted in more favorable improvements in anthropometric indices and insulin sensitivity compared to the calorie restriction alone. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Research Vice-chancellor of Tabriz University of Medical Sciences, Tabriz, Iran, and was registered in the Iranian Registry of Clinical Trials (registration ID: IRCT20140907019082N9 ). PMID: 32782010 [PubMed - in process]
https://link.springer.com/article/10.1007%2Fs00404-020-05730-z
https://www.ncbi.nlm.nih.gov/pubmed/32757043?dopt=Abstract
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MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance.
Arch Gynecol Obstet. 2020 Aug 05;:
Authors: Zhang C, Yu C, Lin Z, Pan H, Li K, Ma H
Abstract
PURPOSE: The present study established microRNA (miRNA) expression profiles for rat ovaries displaying polycystic ovary syndrome (PCOS) with insulin resistance and explored the underlying biological functions of differentially expressed miRNAs.
METHODS: A PCOS with insulin resistance rat model was created by administering letrozole and a high-fat diet. Total RNA was extracted from the ovaries of PCOS with insulin resistance rats and normal rats. Three ovaries from each group were used to identify differentially expressed miRNAs by deep sequencing. A hierarchical clustering heatmap and volcano plot were used to display the pattern of differentially expressed miRNAs. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the potential target genes of the differentially expressed miRNAs and identify their putative biological function. Nine of the differentially expressed miRNAs were selected for validation by Real-time Quantitative PCR (qRT-PCR).
RESULTS: A total of 58 differentially expressed miRNAs were identified in the rat ovaries exhibiting PCOS with insulin resistance compared with control ovaries, including 23 miRNAs that were upregulated and 35 miRNAs that were downregulated. GO and KEGG pathway analyses revealed that the predicted target genes were related to metabolic processes, cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed that miR-3585-5p and miR-30-5p were significantly upregulated and miR-146-5p was downregulated in the ovaries of PCOS with insulin resistance rats compared with the controls.
CONCLUSION: These results indicate that differentially expressed miRNAs in rat ovaries may be involved in the pathophysiology of insulin resistance in PCOS. Our study may be beneficial in establishing miRNAs as novel diagnostic and therapeutic biomarkers for insulin resistance in PCOS.
PMID: 32757043 [PubMed – as supplied by publisher]
https://medicalxpress.com/news/2020-08-young-women-polycystic-ovary-syndrome.html
AUGUST 3, 2020
Young women with polycystic ovary syndrome have raised risk of heart disease
by European Society of Cardiology
https://www.sciencedirect.com/science/article/abs/pii/S0024320520309267?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32745529?dopt=Abstract
miRNAs as a novel clinical biomarker and therapeutic targets in polycystic ovary syndrome (PCOS): A review.
Life Sci. 2020 Jul 31;:118174
Authors: Abdalla M, Deshmukh H, Atkin SL, Sathyapalan T
Abstract
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of the reproductive age. PCOS is commonly manifested as ovulatory dysfunction, clinical and biochemical excess androgen level, and polycystic ovaries. Metabolic sequelae associated with PCOS, including insulin resistance (IR), type 2 diabetes (T2DM), obesity and increased cardiometabolic risk. The underlying pathology of PCOS is not fully understood with various genetic and environmental factors have been proposed. MicroRNAs (miRNAs), are endogenously produced, small non-coding, single-stranded RNAs that capable of regulating gene expression at the post-transcriptional level. Altered miRNAs expression has been associated with various disorders, including T2DM, IR, lipid disorder, infertility, atherosclerosis, endometriosis, and cancer. Given that PCOS also present with similar features, there is an increasing interest to investigate the role of miRNAs in the diagnosis and management of PCOS. In recent years, studies have demonstrated that miRNAs are present in various body fluids, including follicular fluid of women with PCOS. Therefore, it may act as a potential biomarker and could serve as a novel therapeutic target for the diagnosis and treatment of PCOS. This review aims to summarise the up to date research on the relation between miRNAs and PCOS and explore its potential role in the diagnosis and the management of PCOS.
PMID: 32745529 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04493788
https://clinicaltrials.gov/ct2/show/NCT04493788?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=07%2F16%2F2020&lupd_d=14
Condition : Polycystic Ovary Syndrome
Intervention : Other: Blood test, ultrasound and egg retrieval
Sponsor : Universitair Ziekenhuis Brussel
Not yet recruiting
Molecular Basis of PCOS in Oocytes and Surrounding Cells
NCT04493788
Thu, 30 Jul 2020 12:00:00 EDT
Last Update Posted: 07/30/20 07:11AM
https://link.springer.com/article/10.1007%2Fs43032-020-00273-9
https://www.ncbi.nlm.nih.gov/pubmed/32725591?dopt=Abstract
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Ascorbic Acid and Alpha-Tocopherol Contribute to the Therapy of Polycystic Ovarian Syndrome in Mouse Models.
Reprod Sci. 2020 Jul 28;:
Authors: Bafor EE, Uchendu AP, Osayande OE, Omoruyi O, Omogiade UG, Panama EE, Elekofehinti OO, Oragwuncha EL, Momodu A
Abstract
Polycystic ovary syndrome (PCOS) affects up to 10% of women within reproductive ages and has been a cause of infertility and poor quality of life. Alteration in the oxidant-antioxidant profile occurs in PCOS. This study, therefore, investigates the contribution of ascorbic acid (AA) and alpha-tocopherol(ATE) on different PCOS parameters. The mifepristone and letrozole models were used, and young mature female mice were randomly assigned to groups of six per group. On PCOS induction with either mifepristone or letrozole, mice were administered AA and ATE at doses ranging from 10-1000mg/kg to 0.1-1000 mg/kg in the respective models. Vaginal cytology, body weights, and temperature, as well as blood glucose, testosterone, and insulin levels, were measured. Total antioxidant capacity and malondialdehyde levels were analyzed. Determination of gene expression of some reactive oxygen species and histomorphological analysis on the ovaries and uteri were performed. At the end of the experiments, AA and ATE restored reproductive cycling, with AA being more effective. AA and ATE increased fasting blood glucose but had no significant effect on serum insulin levels. AA decreased testosterone levels, but ATE caused slight increases. AA and ATE both increased total antioxidant capacity and decreased malondialdehyde levels. AA and ATE also slightly upregulated the mRNA expressions of catalase, superoxide dismutase, and heme oxygenase 1 mainly. AA and ATE also decreased ovarian weight and mostly resolved cysts in the ovaries and congestion in the uterus. This study has shown that AA and ATE are beneficial in the therapy of PCOS.
PMID: 32725591 [PubMed – as supplied by publisher]
https://www.tandfonline.com/doi/abs/10.1080/14647273.2020.1795574?journalCode=ihuf20
https://www.ncbi.nlm.nih.gov/pubmed/32713212?dopt=Abstract
Related Articles
Anogenital distance and anti-Müllerian hormone combined improves the diagnosis of polycystic ovary syndrome.
Hum Fertil (Camb). 2020 Jul 27;:1-9
Authors: Prieto-Sánchez MT, Hernández-Peñalver AI, Sánchez-Ferrer ML, Mendiola J, Torres-Cantero AM
Abstract
The objective of this study was to assess the accuracy of the combination of anogenital distance (AGD) and anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS). The study included women diagnosed with PCOS and a control group who attended the Clinical University Hospital ‘Virgen de la Arrixaca’ in Murcia (Spain). Serum concentrations of AMH were measured and two AGD measurements were obtained: (i) from the anterior clitoral surface to the upper verge of the anus (AGDAC); and (ii) from the posterior fourchette to the upper verge of the anus (AGDAF). Data were assessed by receiver operator characteristic (ROC) curves. Women with PCOS (n = 126) had significantly larger AGDAC (80.5 ± 11.3 versus 76.0 ± 10.4 mm; p < 0.001) and higher AMH (7.2 ± 4.7 versus 3.1 ± 2.2; p < 0.001) compared to control women (n = 159). Women with serum AMH above 3.8 ng/mL (clinical cut-off used in PCOS) were 9.1 times more likely to have PCOS (95% CI: 5.1-16.2). The area under the ROC curve of combined model of AMH and AGDAC was 0.87 (95% CI: 0.83-0.91). The combined model for predicting PCOS based on AMH and AGDAC has better diagnostic accuracy than that of AMH or AGDAC alone. This model could be useful for clinicians and improve diagnosis and clinical management of these women. PMID: 32713212 [PubMed - as supplied by publisher]
https://rep.bioscientifica.com/view/journals/rep/160/3/REP-19-0501.xml
https://www.ncbi.nlm.nih.gov/pubmed/32716007?dopt=Abstract
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The ovarian stroma as a new frontier.
Reproduction. 2020 Sep;160(3):R25-R39
Authors: Kinnear HM, Tomaszewski CE, Chang FL, Moravek MB, Xu M, Padmanabhan V, Shikanov A
Abstract
Historically, research in ovarian biology has focused on folliculogenesis, but recently the ovarian stroma has become an exciting new frontier for research, holding critical keys to understanding complex ovarian dynamics. Ovarian follicles, which are the functional units of the ovary, comprise the ovarian parenchyma, while the ovarian stroma thus refers to the inverse or the components of the ovary that are not ovarian follicles. The ovarian stroma includes more general components such as immune cells, blood vessels, nerves, and lymphatic vessels, as well as ovary-specific components including ovarian surface epithelium, tunica albuginea, intraovarian rete ovarii, hilar cells, stem cells, and a majority of incompletely characterized stromal cells including the fibroblast-like, spindle-shaped, and interstitial cells. The stroma also includes ovarian extracellular matrix components. This review combines foundational and emerging scholarship regarding the structures and roles of the different components of the ovarian stroma in normal physiology. This is followed by a discussion of key areas for further research regarding the ovarian stroma, including elucidating theca cell origins, understanding stromal cell hormone production and responsiveness, investigating pathological conditions such as polycystic ovary syndrome (PCOS), developing artificial ovary technology, and using technological advances to further delineate the multiple stromal cell types.
PMID: 32716007 [PubMed – in process]
https://clinicaltrials.gov/ct2/show/NCT03252223?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=03%2F14%2F2019&lupd_d=14
Conditions : Polycystic Ovary Syndrome; Healthy; Anovulation; Hyperandrogenism
Intervention : Drug: Recombinant Follicle Stimulating Hormone
Sponsors : University of California, San Diego; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting
Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
NCT03252223
Thu, 17 Aug 2017 12:00:00 EDT
Last Update Posted: 03/28/19 09:23AM
https://clinicaltrials.gov/ct2/show/NCT03252223?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=07%2F10%2F2020&lupd_d=14
Conditions : Polycystic Ovary Syndrome; Healthy; Anovulation; Hyperandrogenism
Intervention : Drug: Recombinant Follicle Stimulating Hormone
Sponsors : University of California, San Diego; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Recruiting
Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
NCT03252223
Thu, 17 Aug 2017 12:00:00 EDT
Last Update Posted: 07/24/20 06:51AM
https://molmed.biomedcentral.com/articles/10.1186/s10020-020-00198-8
https://www.ncbi.nlm.nih.gov/pubmed/32698821?dopt=Abstract
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Electroacupuncture alleviates polycystic ovary syndrome-like symptoms through improving insulin resistance, mitochondrial dysfunction, and endoplasmic reticulum stress via enhancing autophagy in rats.
Mol Med. 2020 Jul 22;26(1):73
Authors: Peng Y, Guo L, Gu A, Shi B, Ren Y, Cong J, Yang X
Abstract
BACKGROUND: Electroacupuncture (EA), a treatment derived from traditional Chinese medicine, can effectively improve hyperandrogenism and insulin resistance in patients with polycystic ovary syndrome (PCOS), however, its underlying mechanisms remain obscure. This study aimed to investigate whether EA could mitigate PCOS-like symptoms in rats by regulating autophagy.
METHODS: A rat model of PCOS-like symptoms was established by subcutaneous injection with dehydroepiandrosterone (DHEA), and then EA treatment at acupoints (ST29 and SP6) was carried out for 5 weeks. To inhibit autophagy in rats, intraperitoneal injection with 0.5 mg/kg 3-MA (an autophagy inhibitor) was performed at 30 min before each EA treatment.
RESULTS: EA intervention alleviated PCOS-like symptoms in rats, which was partly counteracted by the combination with 3-MA. Moreover, DHEA-exposure-induced deficient autophagy in skeletal muscle was improved by EA treatment. EA-mediated improvements in insulin resistance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in PCOS-like rats were counteracted by 3-MA pretreatment. Mechanically, EA attenuated autophagy deficiency-mediated insulin resistance in PCOS-like rats via inactivating mTOR/4E-BP1 signaling pathway.
CONCLUSIONS: Taken together, our findings indicate that EA treatment ameliorates insulin resistance, mitochondrial dysfunction, and ER stress through enhancing autophagy in a PCOS-like rat model. Our study provides novel insight into the mechanisms underlying the treatment of EA in PCOS, which offers more theoretic foundation for its clinical application.
PMID: 32698821 [PubMed – in process]
https://www.news-medical.net/news/20200720/Developing-a-Better-Understanding-of-Polycystic-Ovary-Syndrome-(PCOS).aspx
Developing a Better Understanding of Polycystic Ovary Syndrome (PCOS): Interview with Dr. Andrea Dunaif
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326049/
https://pubmed.ncbi.nlm.nih.gov/32670195/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376399/
https://www.hindawi.com/journals/ecam/2020/3608062/
https://www.ncbi.nlm.nih.gov/pubmed/32733580?dopt=Abstract
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Effects of Electroacupuncture on Ovarian Expression of the Androgen Receptor and Connexin 43 in Rats with Letrozole-Induced Polycystic Ovaries.
Evid Based Complement Alternat Med. 2020;2020:3608062
Authors: Xu G, Zhang A, Liu J, Wang X, Feng J, Chen Y
Abstract
Background: Polycystic ovarian syndrome (PCOS) occurs in women of reproductive age and is often characterized by reproductive and endocrine dysfunction. Androgens play a major role in PCOS, and previous studies reported abnormal expression of Connexin 43 (Cx43) in animal models of PCOS, suggesting an association of Cx43 with PCOS pathogenesis. Experimental and clinical evidence indicated that acupuncture may be a safe and effective approach for treating reproductive and endocrine disorders in women with PCOS. This study aimed to determine the effects of electroacupuncture (EA) on PCOS and its relationship with the expression of the androgen receptor (AR) and Cx43.
Methods: In total, 30 female Sprague Dawley rats (6 weeks old) were randomly divided into three groups: control group, letrozole (LE) group, and LE + EA group. Rats were administered LE solution (1.0 mg/kg) for 21 consecutive days to induce PCOS. For the LE + EA group, additional EA treatment was conducted (2 Hz, 20 min/d) with “Guanyuan” (CV3) for 14 consecutive days. After hematoxylin-eosin staining, the ovarian structure was observed with an optical microscope, and serum levels of the following hormones were examined via enzyme-linked immunosorbent assay (ELISA): testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH); luteinizing hormone (LH), insulin (INS), anti-Müllerian hormone (AMH), and inhibin B (INHB). Fasting blood glucose (FBG) levels were evaluated using glucose oxidase-peroxidase. Ovarian mRNA and protein expressions of AR and Cx43 were determined by real-time RT-PCR and Western blot analysis.
Results: EA was found to restore the cyclicity and ovarian morphology in the PCOS rat model. Serum derived from the LE + EA group showed significant decreases in the levels of T, free androgen index (FAI), LH, LH/FSH ratio, AMH, INHB, and fasting serum insulin (FINS), and significant increases in the levels of E2, FSH, and SHBG. Western blot analysis showed a decreased protein expression of ovarian AR and Cx43; real-time RT-PCR showed reduced expression of ovarian mRNA levels of AR and Cx43.
Conclusions: In conclusion, our results showed that EA can ease hyperandrogenism and polycystic ovary morphology in PCOS rats. Furthermore, EA counteracted the letrozole-induced upregulation of AR and Cx43. These results suggested that acupuncture can break the vicious cycle initiated by excessive androgen secretion and may be an effective treatment method for improving the reproductive and endocrine dysfunction caused by PCOS.
PMID: 32733580 [PubMed]
https://www.degruyter.com/view/journals/reveh/ahead-of-print/article-10.1515-reveh-2020-0032/article-10.1515-reveh-2020-0032.xml
https://www.ncbi.nlm.nih.gov/pubmed/32663175?dopt=Abstract
Related Articles
Bisphenol-A and polycystic ovary syndrome: a review of the literature.
Rev Environ Health. 2020 Jul 14;:
Authors: Kechagias KS, Semertzidou A, Athanasiou A, Paraskevaidi M, Kyrgiou M
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age with reproductive, metabolic and endocrine implications. While the exact pathophysiological mechanisms of the syndrome are unknown, its heterogeneity suggests a multifactorial causal background. In the last two decades, numerous environmental chemicals, including Bisphenol-A (BPA) that is used in the synthesis of polycarbonate plastics, have been proposed as potential contributors to the aetiology of PCOS. This review provides a holistic overview of the available data regarding the possible relation of PCOS with BPA exposure. We have included a total number of 24 studies. Eleven human case-control and 13 animal studies provided data regarding this potential relation. Accumulating evidence suggests that a correlation between high levels of BPA and the presence of PCOS may exist. Contradicting results from human and animal studies, however, render it difficult to conclude on the exact role of BPA in the pathogenesis of PCOS. BPA may constitute a consequence of the syndrome rather than a cause, but further research is still needed to clarify this. Continued efforts to study the early origins of PCOS, using prospective-designed studies, are required to identify the exact effect of BPA on women with PCOS.
PMID: 32663175 [PubMed – as supplied by publisher]
https://www.sciencedirect.com/science/article/abs/pii/S1043466620302040?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32673996?dopt=Abstract
Serum β-Klotho concentrations are increased in women with polycystic ovary syndrome.
Cytokine. 2020 Jul 13;134:155188
Authors: Bednarska S, Fryczak J, Siejka A
Abstract
Polycystic ovary syndrome (PCOS) is a significant cause of menstrual disorders and infertility in women. The aim of this study was to evaluate the levels of Klotho expression in women with polycystic ovary syndrome. The study involved 67 patients with PCOS, as well as 18 controls. Serum levels of FGF19, FGF21 and β-Klotho were measured by ELISA technique. The blood samples were obtained between days 2 and 7 of menstrual cycle. The concentrations of β-Klotho, FGF19 and FGF21 were significantly increased in patients with PCOS; and appear to be statistically significant predictors of PCOS incidence. FGF19 (p = 0.031, OR = 1.01), exact β-Klotho levels (p = 0.022, OR = 1.01) and β-Klotho beyond the reference range (p = 0.008, OR = 4.66) were the most strongly correlated with the diagnosis of PCOS. In conclusion, FGF19, FGF21 and β-Klotho are increased in PCOS, and elevated β-Klotho concentration may become an useful diagnostic test for this disease. However, additional studies are required to further substantiate this observation.
PMID: 32673996 [PubMed – as supplied by publisher]
https://www.aging-us.com/article/103602/text
https://www.ncbi.nlm.nih.gov/pubmed/32651991?dopt=Abstract
Depletion of exosomal circLDLR in follicle fluid derepresses miR-1294 function and inhibits estradiol production via CYP19A1 in polycystic ovary syndrome.
Aging (Albany NY). 2020 Jul 10;12:
Authors: Huang X, Wu B, Chen M, Hong L, Kong P, Wei Z, Teng X
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive women and is characterized by polycystic ovaries, hyperandrogenism and chronic anovulation. Abnormal folliculogenesis is considered as a common characteristic of PCOS. Our aim is to identify the altered circRNA expression profile in exosomes isolated from follicular fluid (FF) of PCOS patients to investigate the molecular function of exosomal circRNA, as a vital mediator in follicular microenvironment, in the aetiology and pathobiology of PCOS. In this study, the circRNA expression profile of FF exosomes were compared between PCOS and control patients by RNA sequencing (N=5 vs 5). Sixteen circRNAs showed significantly different expression. GO and KEGG pathway analyses indicated that their parental genes were enriched in PCOS-related pathways, including ovarian steroidogenesis, aldosterone synthesis and secretion, and Jak-STAT signaling. Among sixteen differentially expressed circRNAs, hsa_circ_0006877 (circLDLR) was processed from its parental LDLR (low density lipoprotein receptor) transcript, which participated in ovarian steroidogenesis. Its depletion in PCOS FF exosomes was further verified in an additional cohort (N=25 vs 25) by qRT-PCR. And a circLDLR-miR-1294-CYP19A1 competing endogenous RNA (ceRNA) network was predicted by cytoscape software, and confirmed by luciferase assay and correlative expression in the cumulus cells of PCOS patients. Mechanistically, the intercellular transfer of functional circLDLR assay and its withdrawal experiments in KGN cells showed that depleting circLDLR in exosomes increased miR-1294 expression and inhibited CYP19A1 expression in recipient cells, as well as reduced their estrogen (E2) secretion. Our findings revealed a ceRNA network of circLDLR and provided new information on abnormal follicle development in PCOS.
PMID: 32651991 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03674385?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=02%2F18%2F2019&lupd_d=14
Condition : Clomiphene Citrate Resistant Polycystic Ovary Syndrome
Interventions : Dietary Supplement: vitamin E; Drug: Metformin; Drug: Clomiphene Citrate
Sponsors : Ain Shams University; Misr University for Science and Technology
Recruiting
Efficacy of Vit E in PCOS Resistant to Clomiphene Citrate
NCT03674385
Mon, 17 Sep 2018 12:00:00 EDT
Last Update Posted: 03/04/19 09:37AM
https://www.mdpi.com/1422-0067/21/14/4853
https://www.ncbi.nlm.nih.gov/pubmed/32659951?dopt=Abstract
Related Articles
Metabolomic Insight into Polycystic Ovary Syndrome-An Overview.
Int J Mol Sci. 2020 Jul 09;21(14):
Authors: Rajska A, Buszewska-Forajta M, Rachoń D, Markuszewski MJ
Abstract
Searching for the mechanisms of the polycystic ovary syndrome (PCOS) pathophysiology has become a crucial aspect of research performed in the last decades. However, the pathogenesis of this complex and heterogeneous endocrinopathy remains unknown. Thus, there is a need to investigate the metabolic pathways, which could be involved in the pathophysiology of PCOS and to find the metabolic markers of this disorder. The application of metabolomics gives a promising insight into the research on PCOS. It is a valuable and rapidly expanding tool, enabling the discovery of novel metabolites, which may be the potential biomarkers of several metabolic and endocrine disorders. The utilization of this approach could also improve the process of diagnosis and therefore, make treatment more effective. This review article aims to summarize actual and meaningful metabolomic studies in PCOS and point to the potential biomarkers detected in serum, urine, and follicular fluid of the affected women.
PMID: 32659951 [PubMed – in process]
https://clinicaltrials.gov/ct2/show/NCT04452968
https://clinicaltrials.gov/ct2/show/NCT04452968?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=06%2F17%2F2020&lupd_d=14
Conditions : Polycystic Ovarian Syndrome; Weight Loss; Intermittent Fasting
Interventions : Behavioral: intermittent fasting; Behavioral: Caloric restriction
Sponsors : Karachi Medical and Dental College; Aziz Medical Center
Recruiting
Comparison of Intermittent Fasting and Caloric Deficit for Weight Loss in Women With Polycystic Ovarian Syndrome
NCT04452968
Wed, 01 Jul 2020 12:00:00 EDT
Last Update Posted: 07/01/20 07:49AM
https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20200995/225735/Methylenetetrahydrofolate-reductase-gene
https://watermark.silverchair.com/bsr-2020-0995.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAABJgwggSUBgkqhkiG9w0BBwagggSFMIIEgQIBADCCBHoGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM11Airg2PZo1kF5IYAgEQgIIESyTQOK5UkBFpeIMU3inOQlO5L4tx9Nqd4uGmS9rhzSb0lNYR4mpWjnYSSnaAH_CojMSq_jZSqYHrZVIrottT-jMf14goMOXPAxgmqMvvPNqpLn4n-y2av-p6KA__tz_-gQoycolAeE-bU0Zh19wuOq9VdEiCOMEE_Zuw6hx3wjSUN7m7KjDFGhJXjNcw3nyInomQPfQhQnbGtheFj8bSfobCg8iEri0IdzpwFmU87-zf5Fm4wU95X3jaobAEVIB7VxPLFjmm9NogPTWhJcRidrGPGIhyBgiN6Tup7_cIdsbr9l63OVNablDgnudVtuUOvH4zosRafSoa0jMiBR28ZGDUUMdNjQjmLMSnOmeQ97nzqrsYdxO3dOwWeigl8F2FNrQL8AsbiyKWZ6Wrtyo3Q2uU3bUgnLtcTo3wRGi9uRqQ5LtvIb9LzoIKPau28r9oJ9tivzRoaIjbXhB-jOYsH7adyR8wwOHF1baTrXEgykTYrs89sXuy3g_SubW_A3yXQDe4e_xiAuy_aukGWsWu3pPKsWLBB-dgD5HN5vIgec-ehw90toq5UznNpbvWjJvEXLu92lnHW6EuC6tVoNXYFNcW1jb1WU8nzYjsJNtRk6rHNDg-JhykDJw1MNMuraAJG_2vCr9740OoKonrS0sGJHtWMKgM8-qa47SqrJxiaoNSzGScRyFudI4jQOY8gX_EoRxNQAmiJUFX_pIdArOlzUWWY-fc7GUg7CEdAg8v1GPEepLqH4h7sHFwCNw_Yaweh1EW8yqQ6ld99ms25A2NkEMU510ODd-Cp3kLrg3vAGK-u4UmIJpvVYC4eNXrrGZnajijRRcuiGEvuJwBvy0cXHqiE8RKIEB6fNEQKJioEWIGWVQ2IUXbdD5Wohu2KQM5Z_BpBqT0uzmc0OopJ7omikHVxuPuwNEKw9U3c-YE4pKx2L9G61WqHleopwJFOn1iSfsDnsItxor9zOfspAySfqp6wKEKFANoG0fhP2-xqlSgkeO0ZPKRXAGByJYEfGoXyrW3cm-TaiUF5TA-RLNjEKqWIyuAtbvfnnzxj1F6HBCIi6vl9577ZC8J6eZceEnDs3IF-w9vZK9o00F8uqTjGwljmOkiq_geKF3plyYEhpo0LUwMC_OTVXgVpdFKermkuCR1DgLctNJ6GebR7y4PDB3DhhlROxw_T9pgFxHbXEWKZC7xZ6bVw8m4rciMusCgPUWokuct–QT2lqCvSDhmjOzBsGgjW4uAJl1loQ-xzrCQa_KW3TRmgA5HvVXEboIRqAnBbw3OlbHhGHna98SzSQkpX7URPZndQXIqyV336w5BYFLaVdtDv-CcrPJkwlNBrphU-mjUEaYwbHjog1eLYInqrZnszQmLnhBuMQzWJI8VsNuOPdGLknqQSrx-o9O9pg0p_JPztinQINcJprrH4z24JlZdS0P9SYoCHNb5rqJQoSXQgdlWlY29tQ
https://www.ncbi.nlm.nih.gov/pubmed/32639550?dopt=Abstract
Methylenetetrahydrofolate reductase gene polymorphisms in the risk of polycystic ovary syndrome and ovarian cancer.
Biosci Rep. 2020 Jul 08;:
Authors: Xiong Y, Bian C, Lin X, Wang X, Xu K, Zhao X
Abstract
Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) in hormone metabolism pathways might cause metabolic disturbances and contribute to the development of polycystic ovary syndrome (PCOS) and ovarian cancer, but the published studies were inconsistent. The aim of this study was to evaluate the MTHFR C677T (rs1801133) and A1298C (rs1801131) gene polymorphisms in the risk of PCOS and ovarian cancer by meta-analysis. A comprehensive electronic search was conducted in databases for studies published from 1995 to 2020. The pooled ORs were calculated by Revman 5.2 software. Twenty-nine articles including 45 case-control studies were included. We found that MTHFR C677T polymorphisms were correlated with elevated PCOS risk (TT vs. CT+CC: OR=1.41, 95%CI=1.20-1.67; TT+CT vs. CC: OR=1.54, 95%CI=1.07-2.22; CT vs. CC+TT: OR=1.18, 95%CI-1.04-1.33; TT vs. CC: OR=1.47, 95%CI=1.03-2.11; T vs. C: OR=1.25, 95%CI=1.06-1.47), which were more obvious in Middle Eastern subgroup. MTHFR A1298C polymorphisms were also associated with overall PCOS susceptibility (CC vs. AC+AA: OR=2.55, 95%=1.61-4.03; CC+AC vs. AA: OR=1.84, 95%CI=1.04-3.28; CC vs. AA: OR=2.66, 95%CI=1.68-4.22; C vs. A: OR=1.67, 95%CI=1.03-2.71), which were mainly reflected in Asian subjects. For ovarian cancer, MTHFR C677T polymorphisms were only related with elevated ovarian cancer risk in Asian population, while no significant association was found for A1298C polymorphisms. This meta-analysis suggested that MTHFR C677T and MTHFR A1298C polymorphisms were correlated with elevated PCOS risk. MTHFR C667T only posed a higher risk for ovarian cancer in Asians instead of other populations, while MTHFR A1298C polymorphisms were not related to ovarian cancer risk. Further studies are needed to validate the conclusion.
PMID: 32639550 [PubMed – as supplied by publisher]
https://www.frontiersin.org/articles/10.3389/fphys.2020.00606/full
https://www.ncbi.nlm.nih.gov/pubmed/32733258?dopt=Abstract
Related Articles
Exercise Interventions in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.
Front Physiol. 2020;11:606
Authors: Patten RK, Boyle RA, Moholdt T, Kiel I, Hopkins WG, Harrison CL, Stepto NK
Abstract
Background: Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive and metabolic manifestations. Exercise training has consistently been found to result in improved clinical outcomes in women with PCOS, but shortfalls with exercise prescription are evident. The aim of this systematic review and meta-analysis was to identify exercise intervention characteristics that provide favourable outcomes in women with PCOS. Methods: A systematic review of published literature was conducted using EBSCOhost and Ovid Medline up to May 2019. The review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines as per our PROSPERO protocol (CRD42018088367). Randomised controlled trials, non-randomised controlled trials, and uncontrolled trials that evaluated an exercise intervention of at least moderate intensity in women with PCOS were included. Meta-analyses were performed using general linear mixed modelling and Bayesian inferences about effect magnitudes. Results: Thirty-three articles were identified for systematic review of which 19 were meta-analysed. Intervention duration ranged from 6 to 26 weeks. A total number of 777 women were included in the meta-analysis. The meta-analysis found that improvements in health outcomes are more dependent on exercise intensity rather than dose. Fixed effects analysis reported a moderate increase in VO2peak (24.2%; 90% CL, 18.5-30.1), and small reductions in HOMA-IR (-36.2%; 90% CL, -55.3 to -9.0), and waist circumference (-4.2%; 90% CL -6.0 to -2.3) as a result of vigorous intensity exercise. These results are confirmed in the predicted analysis which reported the greatest improvements in VO2peak, BMI, and waist circumference after vigorous intensity exercise alone or when combined with diet, particularly for women with clinically adverse baseline values. Conclusions: Exercise training in the management of PCOS is becoming more common. Results from our analysis support the use of exercise and suggest that vigorous intensity exercise may have the greatest impact on cardiorespiratory fitness, body composition, and insulin resistance. Our results indicate that, a minimum of 120 min of vigorous intensity per week is needed to provide favourable health outcomes for women with PCOS with studies of longer duration required to evaluate outcomes with sustained exercise.
PMID: 32733258 [PubMed]
https://journals.sagepub.com/doi/10.1177/2042018820938305
https://www.ncbi.nlm.nih.gov/pubmed/32670541?dopt=Abstract
Related Articles
A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome.
Ther Adv Endocrinol Metab. 2020;11:2042018820938305
Authors: Abdalla MA, Deshmukh H, Atkin S, Sathyapalan T
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.
PMID: 32670541 [PubMed]
https://www.sciencedirect.com/science/article/abs/pii/S1043466620302039?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32645538?dopt=Abstract
The hallmark of pro- and anti-inflammatory cytokine ratios in women with polycystic ovary syndrome.
Cytokine. 2020 Jul 06;134:155187
Authors: Tosatti JAG, Sóter MO, Ferreira CN, Silva IFO, Cândido AL, Sousa MO, Reis FM, Gomes KB
Abstract
Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrinopathy considered to be the most common metabolic disorder in women of reproductive age. Women with PCOS present with an increased risk of noncommunicable diseases (NCDs), especially low-grade chronic inflammation mediated by proinflammatory cytokines, and insulin resistance. This study aimed to investigate cytokine levels and their ratios in PCOS women compared to a healthy control group. This study evaluated 97 women with PCOS and 99 healthy women as controls. The PCOS diagnosis was performed according to ESHRE/ASRM. Plasma cytokines were evaluated by flow cytometry. We observed lower TNF levels, and decreased TNF/IL-6, TNF/IL-2, and TNF/IL-4 ratios in PCOS patients compared to the control group (p < 0.05). These results indicate an imbalance between pro- and anti-inflammatory cytokines, with prominent counter-regulatory cytokine production. These changes may be important in explaining the phenotypes present in PCOS and to direct better interventions for patients with this syndrome. PMID: 32645538 [PubMed - as supplied by publisher]
https://academic.oup.com/jcem/article-abstract/doi/10.1210/clinem/dgaa425/5867491?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/32621748?dopt=Abstract
Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome.
J Clin Endocrinol Metab. 2020 Jul 04;:
Authors: Shang Y, Zhou H, Hu M, Feng H
Abstract
OBJECTIVE: The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice.
DESIGN: The search was conducted in eight databases through June 30, 2019. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A random-effect model was adopted to calculate the overall effects.
RESULTS: A total of 19 trials (1193 participants) were included. The analysis showed that diet was significantly related to improvements in IR and body composition (e.g., homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin (FINS), fasting plasma glucose (FPG), body mass index (BMI), weight, and waist circumference (WC)) in PCOS patients. The Dietary Approaches to Stop Hypertension (DASH) diet and calorie-restricted diets might be the optimal choices for reducing IR and improving body composition, respectively, in the PCOS population. Additionally, the effects were associated with the course of treatment. The longer the duration, the greater the improvement was. Compared with metformin, diet was also advantageous for weight loss (including BMI and weight) and had the same effects on insulin regulation.
CONCLUSION: Overall, our findings suggest that diet is an effective, acceptable and safe intervention for relieving IR, and professional dietary advice should be offered to all PCOS patients.
PMID: 32621748 [PubMed – as supplied by publisher]
https://link.springer.com/article/10.1007/s10815-020-01865-9
https://www.ncbi.nlm.nih.gov/pubmed/32623663?dopt=Abstract
The impact of polycystic ovary syndrome and body mass index on the absorption of recombinant human follicle stimulating hormone.
J Assist Reprod Genet. 2020 Jul 04;:
Authors: Lee MS, Lanes A, Dolinko AV, Bailin A, Ginsburg E
Abstract
PURPOSE: Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls.
METHODS: Fourteen women with PCOS aged 18-42 years old with a BMI of 18.5-24.9 kg/m2 (normal) or 25.0-40.0 kg/m2 (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225 IU rFSH and underwent serial blood draws over 72 h.
RESULTS: Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72 h when compared with overweight/obese PCOS subjects (183.3 vs 139.8 IU*h/L, p = 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8 IU*h/L, p < 0.0001). Within overweight/obese subjects, those with PCOS had a significantly higher AUC FSH compared with normo-ovulatory controls (p = 0.0002). Lean PCOS subjects similarly had the highest AUC of baseline-corrected estradiol (6095 pg h/mL), compared with lean normo-ovulatory subjects (1931 pg h/mL, p < 0.0001) and overweight/obese PCOS subjects (2337 pg h/mL, p < 0.0001). CONCLUSION: Lean PCOS subjects exhibited significantly higher baseline-corrected FSH and estradiol levels following rFSH injection compared with overweight/obese PCOS subjects with similar ovarian reserve markers. Amongst overweight/obese subjects, those with PCOS had significantly higher FSH and E2 levels when compared with normo-ovulatory controls. PMID: 32623663 [PubMed - as supplied by publisher]
https://www.pharmacytimes.com/publications/issue/2020/June2020/women-with-autoimmune-thyroid-disease-have-higher-risk-of-pcos
Women With Autoimmune Thyroid Disease Have Higher Risk of PCOS
2020-07-03 14:00:00
https://www.sciencedirect.com/science/article/abs/pii/S0378427420303040?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32629074?dopt=Abstract
High-refined carbohydrate diet leads to polycystic ovary syndrome-like features and reduced ovarian reserve in female rats.
Toxicol Lett. 2020 Jul 03;:
Authors: Niño OMS, da Costa CS, Torres KM, Zanol JF, Freitas-Lima LC, Miranda-Alves L, Graceli JB
Abstract
Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.
PMID: 32629074 [PubMed – as supplied by publisher]
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29912
https://www.ncbi.nlm.nih.gov/pubmed/32617971?dopt=Abstract
Related Articles
Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome.
J Cell Physiol. 2020 Jul 02;:
Authors: Rostamtabar M, Esmaeilzadeh S, Tourani M, Rahmani A, Baee M, Shirafkan F, Saleki K, Mirzababayi SS, Ebrahimpour S, Nouri HR
Abstract
Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause inflammatory response and maintenance of the inflammation state in adipocytes by augmented production of inflammatory cytokines, monocyte chemoattractant proteins, and recruitment of the immune cell. Therefore, the PCOS can be related to a low-grade inflammation state and inflammatory markers. Investigating the inflammatory processes and mediators that contribute to the commencement and development of PCOS can be a critical step for better understanding the pathophysiology of the disease and its treatment through inhibition or control of related pathways. In the present review, we discuss the pathophysiological roles of chronic low-grade inflammation mediators including inflammasome-related cytokines, interleukin-1β (IL-1β), and IL-18 in PCOS development.
PMID: 32617971 [PubMed – as supplied by publisher]
https://pubmed.ncbi.nlm.nih.gov/32627151/
https://www.ncbi.nlm.nih.gov/pubmed/32627151?dopt=Abstract
https://journals.viamedica.pl/ginekologia_polska/article/view/GP.2020.0057
https://journals.viamedica.pl/ginekologia_polska/article/view/65892
Circulating omentin-1 levels and inflammation in polycystic ovary syndrome.
Ginekol Pol. 2020;91(6):308-312
Authors: Franik G, Sadlocha M, Madej P, Owczarek A, Skrzypulec-Plinta V, Plinta R, Chudek J, Olszanecka-Glinianowicz M
Abstract
OBJECTIVES: The aim of the study was to analyze interrelation between plasma omentin-1 levels and nutritional status and inflammation in PCOS.
MATERIAL AND METHODS: A cross-sectional study involving 86 PCOS (47 obese) and 72 Non-PCOS women (41 obese) determined anthropometric parameters and body composition. Serum glucose, insulin and omentin-1, TNF-α, sTNFRs, IL-6 and sR-IL6 were measured in the fasting state.
RESULTS: Plasma omentin-1 levels were significantly lower in the PCOS than in the Non-PCOS group and both corresponding normal weight and obese subgroups. In three analyzed least-angle regression (LARS) models the lower plasma omentin- 1 levels was associated with PCOS occurrence, higher circulating TNF-α and lower IL-6 levels.
CONCLUSIONS: Suppressed omentin-1 levels in PCOS are characteristic for this disturbance and proinflammatory cytokines are factors modifying secretion of this adipokine.
PMID: 32627151 [PubMed – in process]
https://journals.sagepub.com/doi/10.1177/2633494120913032
https://www.ncbi.nlm.nih.gov/pubmed/32656532?dopt=Abstract
Related Articles
Controversies in the diagnosis of polycystic ovary syndrome.
Ther Adv Reprod Health. 2020 Jan-Dec;14:2633494120913032
Authors: Rao P, Bhide P
Abstract
Polycystic ovary syndrome is a common endocrinological condition which is found to be prevalent in 5-10% of women of reproductive age. Historically, a combination of anovulation and androgen excess was considered a hallmark in the diagnosis of polycystic ovary syndrome. Addition of ultrasound features of polycystic ovary syndrome has improved the detection of variation in the polycystic ovary syndrome phenotype. Despite the widespread use of consensus diagnostic criteria, there remain several unresolved controversies in the diagnosis of polycystic ovary syndrome. Difficulty arises in methods of assessment and types of androgens to be measured to detect biochemical hyperandrogenism, setting a cut-off value for the diagnosis of clinical hyperandrogenism, setting an ultrasound threshold of antral follicle count to diagnose polycystic ovaries and also diagnosing this condition in adolescence where there is no clear definition for ‘irregular cycles’. This article looks at various controversies in the diagnosis of polycystic ovary syndrome.
PMID: 32656532 [PubMed]
https://www.mdpi.com/1422-0067/21/13/4572
https://pubmed.ncbi.nlm.nih.gov/32604999/
https://www.ncbi.nlm.nih.gov/pubmed/32604999?dopt=Abstract
Related Articles
Involvement of ACE2/Ang-(1-7)/MAS1 Axis in the Regulation of Ovarian Function in Mammals.
Int J Mol Sci. 2020 Jun 27;21(13):
Authors: Domińska K
Abstract
In addition to the classic, endocrine renin-angiotensin system, local renin-angiotensin system (RAS) has been documented in many tissues and organs, including the ovaries. The localization and functional activity of the two opposing axes of the system, viz. ACE1/Ang II/AT1 and ACE2/Ang-(1-7)/MAS1, differs between animal species and varied according to the stage of follicle development. It appears that the angiotensin peptides and their receptors participate in reproductive processes such as folliculogenesis, steroidogenesis, oocyte maturation, and ovulation. In addition, changes in the constituent compounds of local RAS may contribute to pathological conditions, such as polycystic ovary syndrome, ovarian hyperstimulation syndrome, and ovarian cancer. This review article examines the expression, localization, metabolism, and activity of individual elements of the ACE2/Ang-(1-7)/MAS1 axis in the ovaries of various animal species. The manuscript also presents the relationship between the secretion of gonadotropins and sex hormones and expression of Ang-(1-7) and MAS1 receptors. It also summarizes current knowledge regarding the positive and negative impact of ACE2/Ang-(1-7)/MAS1 axis on ovarian function.
PMID: 32604999 [PubMed – in process]
https://www.medicinenet.com/discovery_make_pcos_diagnosis_treatment_simpler-news.htm
Genetic Discovery May Simplify PCOS Diagnosis, Treatment
https://www.wellandgood.com/good-advice/pcos-subtypes/
New Research Shows a New Way To Classify PCOS, Paving the Way for Better Diagnosis and Treatment
https://journals.sagepub.com/doi/10.1177/2042018820934319
https://www.ncbi.nlm.nih.gov/pubmed/32637065?dopt=Abstract
Related Articles
Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome.
Ther Adv Endocrinol Metab. 2020;11:2042018820934319
Authors: Kempegowda P, Melson E, Manolopoulos KN, Arlt W, O’Reilly MW
Abstract
Polycystic ovary syndrome (PCOS) has been traditionally perceived as a reproductive disorder due to its most common presentation with menstrual dysfunction and infertility. However, it is now clear that women with PCOS are at increased risk of metabolic dysfunction, from impaired glucose tolerance and type 2 diabetes mellitus to nonalcoholic fatty liver disease and cardiovascular disease. PCOS is characterised by androgen excess, with cross-sectional data showing that hyperandrogenism is directly complicit in the development of metabolic complications. Recent studies have also shown that C11-oxy C19 androgens are emerging to be clinically and biochemically significant in PCOS, thus emphasising the importance of understanding the impact of both classic and C11-oxy C19 androgens on women’s health. Here we discuss androgen metabolism in the context of PCOS, and dissect the role played by androgens in the development of metabolic disease through their effects on metabolic target tissues in women.
PMID: 32637065 [PubMed]
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003132
Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis
Matthew Dapas,Frederick T. J. Lin,Girish N. Nadkarni,Ryan Sisk,Richard S. Legro,Margrit Urbanek,M. Geoffrey Hayes ,Andrea Dunaif
Published: June 23, 2020https://doi.org/10.1371/journal.pmed.1003132
https://medicalxpress.com/news/2020-06-distinct-subtypes-polycystic-ovary-syndrome.html
Researchers identify distinct subtypes of polycystic ovary syndrome with novel genetic associations
https://www.mdpi.com/2077-0383/9/6/1961
https://www.ncbi.nlm.nih.gov/pubmed/32585861?dopt=Abstract
Related Articles
Is There a Bidirectional Association between Polycystic Ovarian Syndrome and Periodontitis? A Systematic Review and Meta-analysis.
J Clin Med. 2020 Jun 23;9(6):
Authors: Machado V, Escalda C, Proença L, Mendes JJ, Botelho J
Abstract
Polycystic ovary syndrome (PCOS) has reproductive and metabolic properties that may be linked to periodontitis (PD). This study aimed to update and render a robust critical assessment on all evidence linking PCOS and PD, and appraising a hypothetical bidirectional association. Five databases (PubMed, Scholar, EMBASE, Web of Science and CENTRAL) were searched up to May 2020. Case-control and cohort studies on the association of PCOS and PD were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses of standardized mean difference (SMD) and risk ratio (RR) were performed. We followed Strength of Recommendation Taxonomy (SORT) to appraise the strength and quality of the evidence. Twelve case-controls fulfilled the inclusion criteria (876 with PCOS and 48170 healthy controls), all scored as having a low risk of bias. Meta-analysis revealed that PCOS females have 28% more risk towards PD, and PD females have 46% more risk to have PCOS. PCOS females with PD had higher gum bleeding, periodontal pocket depth and clinical attachment loss than non-PCOS females with PD. Populations with undefined periodontal status contribute to underestimated results. On the basis of the available evidence, it is possible to assume a bidirectional link between PCOS and PD. That is, PCOS increases by 28% the risk of having PD and in the same fashion, PD increases by 46% the risk of having PCOS. Furthermore, women with PCOS were associated with worsening clinical characteristics and inflammation of PD. These findings suggest that PCOS and PD may be linked. Hence, further prospective and clinical trial studies with nonsurgical periodontal therapy are necessary to clarify the existence of an increased risk of PCOS in women with PD and vice-versa.
PMID: 32585861 [PubMed]
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-020-00994-8
Exploratory study of a screening measure for polycystic ovarian syndrome, quality of life assessment, and neuropsychological evaluation
Michael J. Boivin, Farnaz Fatehi, Amy E. Phillips-Chan, Julia R. Richardson, Amanda N. Summers & Steven A. Foley
BMC Women’s Health volume 20, Article number: 132 (2020) Cite this article
314 Accesses
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http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7321515/
https://www.hindawi.com/journals/ije/2020/1484321/
https://www.ncbi.nlm.nih.gov/pubmed/32655632?dopt=Abstract
Related Articles
GLP-1/GLP-1R Signaling Regulates Ovarian PCOS-Associated Granulosa Cells Proliferation and Antiapoptosis by Modification of Forkhead Box Protein O1 Phosphorylation Sites.
Int J Endocrinol. 2020;2020:1484321
Authors: Sun Z, Li P, Wang X, Lai S, Qiu H, Chen Z, Hu S, Yao J, Shen J
Abstract
As the major cause of female anovulatory infertility, polycystic ovary syndrome (PCOS) affects a great proportion of women at childbearing age. Although glucagon-like peptide 1 receptor agonists (GLP-IRAs) show therapeutic effects for PCOS, its target and underlying mechanism remains elusive. In the present study, we identified that, both in vivo and in vitro, GLP-1 functioned as the regulator of proliferation and antiapoptosis of MGCs of follicle in PCOS mouse ovary. Furthermore, forkhead box protein O1 (FoxO1) plays an important role in the courses. Regarding the importance of granulosa cells (GCs) in oocyte development and function, the results from the current study could provide a more detailed illustration on the already known beneficial effects of GLP-1RAs on PCOS and support the future efforts to develop more efficient GLP-1RAs for PCOS treatment.
PMID: 32655632 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT00914823
https://clinicaltrials.gov/ct2/show/NCT00914823?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=06%2F06%2F2019&lupd_d=14
Conditions : Hypogonadotropic Hypogonadism; Kallmann Syndrome; GnRH Deficiency; PCOS; Polycystic Ovarian Syndrome; Hyperprolactinemia
Interventions : Drug: kisspeptin 112-121; Drug: GnRH
Sponsor : Massachusetts General Hospital
Recruiting
Administration of Kisspeptin to Subjects With Reproductive Disorders
NCT00914823
Fri, 05 Jun 2009 12:00:00 EDT
Last Update Posted: 06/20/19 09:40AM
https://clinicaltrials.gov/ct2/show/NCT03951077
https://clinicaltrials.gov/ct2/show/NCT03951077?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=05%2F01%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Drug: Elagolix; Drug: Placebo
Sponsor : AbbVie
Not yet recruiting
Study of the Safety and Efficacy of Elagolix in Women With Polycystic Ovary Syndrome
NCT03951077
Wed, 15 May 2019 12:00:00 EDT
Last Update Posted: 05/15/19 07:42AM
Project Number: 1R01HD100630-01 Contact PI / Project Leader: URBANEK, MARGRIT
Title: AMH SIGNALING PATHWAY VARIATION IN PCOS Awardee Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Abstract Text:
Polycystic Ovary Syndrome (PCOS) is a complex disorder with endocrine, reproductive, and metabolic features. With a prevalence of 5-15%, it is the most common form of infertility in reproductive age women. Women with PCOS are also at increased risk of developing obesity, insulin resistance and Type 2 Diabetes. Consequently, PCOS has a strong negative impact on the health of the population contributing >$5 billion to the healthcare burden in the US annually. It is characterized by elevated testosterone levels, irregular periods, and polycystic ovaries. Although PCOS is highly heritable, traditional genetic approaches have identified <5% of all the genetic variation contributing to this syndrome. Rare genetic variants and regulatory element variation may account for this “missing” heritability. In an unbiased whole genome sequencing screen of women with PCOS, we identified missense mutations in the anti-Müllerian hormone gene (AMH). AMH is strong candidate gene for PCOS. It is critical to two central features of PCOS: ovarian follicle recruitment and development and androgen production. AMH is elevated in PCOS and has been proposed as a biomarker for PCOS. In follow-up studies, we identified a total of 37 rare coding and regulatory variants in AMH and its type 2 receptor (AMHR2). These variants had significantly reduced signaling capacity in 6.7% of our cohort. No variants with impaired activity were observed in controls and no variants with increased signaling activity were observed in PCOS or reproductively normal womrn. Our results are highly significant relative to reproductively normal women (χ2=18.0, p=2.20E-05) and to non-Finnish European population-based controls (p < 10-8). Our findings are the first identification of functionally validated variants for PCOS and provide strong evidence for a critical role of the AMH signaling cascade in PCOS. However, to date we have only comprehensibly screened AMH and its receptor AMH. Given that most genes are believed to impact disease risk through highly connected cellular networks, it is our overarching hypothesis that other members of the AMH signaling cascade are also impaired in PCOS To ascertain which components of the AMH signaling cascade are impaired in PCOS and how they impact PCOS subphenotypes, we will apply innovative, state-of-the-art genetic, molecular, and bioinformatic approaches. We will create a comprehensive catalog of putative causal variants in ~30 members of the AMH signaling cascade in multiethnic PCOS cohort and determined the functional consequences of these variants in PCOS and the general population. Collectively, these studies will be the first comprehensive evaluation of functional genetic variation of this critical signaling cascade in PCOS, ii. elucidate the role of members of the AMH signaling cascade in PCOS and female reproduction in general, and iii. define the molecular mechanisms that underlie phenotypic heterogeneity of PCOS identifying PCOS subtypes leading to improved treatment options. These studies are thus a critical step towards the successful implementation of Precision Medicine in the context of PCOS and female reproduction.
Public Health Relevance Statement:
Polycystic ovary syndrome (PCOS) is the most common form of annovulatory infertility of reproductive age women affecting 5-10% of reproductive age women and contributing >$5 billion to the healthcare burden in the US annually. We have identified functional variants in the AMH and AMHR2 genes that are very strongly associated with PCOS and identify a PCOS sub-phenotypic. The goal of this proposal is to identify the function of PCOS causal variants in the broader AMH signaling pathway which will explain the molecular basis and phenotypic heterogeneity of PCOS and the successful implementation of Precision Medicine.
Project Terms:
Affect; Age; Amenorrhea; AMHR2 gene; Androgens; Antral; Aromatase; biobank; Bioinformatics; Biological Assay; Biological Markers; Candidate Disease Gene; Catalogs; causal variant; Code; cohort; Complex; CYP11A1 gene; CYP17A1 gene; Data; dehydroepiandrosterone; Development; Disease; disorder risk; Down-Regulation; Electronic Medical Records and Genomics Network; Endocrine; epigenetic variation; Estradiol; Estrone; Etiology; European; Evaluation; Female; folliculogenesis; Follow-Up Studies; Gene Expression Profile; Gene Frequency; General Population; Genes; Genetic; genetic approach; Genetic Databases; Genetic Transcription; genetic variant; Genetic Variation; genome sequencing; Goals; granulosa cell; Growth; Healthcare; Heritability; Heterogeneity; Hormonal; Hormones; Hyperandrogenism; Impairment; improved; in silico; Infertility; innovation; Insulin Resistance; Link; loss of function; Medical center; Medical Records; member; men; Metabolic; Microfluidics; Minor; Missense Mutation; Modeling; Molecular; mRNA Expression; mullerian-inhibiting hormone; Mullerian-inhibiting substance receptor; next generation sequencing; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oligomenorrhea; Ovarian; Ovarian Follicle; Participant; Periodicity; Phenotype; Polycystic Ovary Syndrome; population based; population health; precision medicine; Prevalence; Production; Progesterone; protein expression; receptor; recruit; Regulation; Regulatory Element; Reporting; Reproduction; reproductive; Risk; Role; Signal Transduction; Signaling Protein; Steroid biosynthesis; support network; Syndrome; Testing; Testosterone; theca cell; Tissues; United States National Institutes of Health; Untranslated RNA; Variant; whole genome; Woman
Contact PI Information: Program Official Information: Other PI Information:
Name: URBANEK, MARGRIT
Email: Click to view contact PI email address
Title: ASSISTANT PROFESSOR Name: TAYMANS, SUSAN
Email: Click to view PO email address Not Applicable
Organization: Department / Educational Institution Type: Congressional District:
Name: NORTHWESTERN UNIVERSITY AT CHICAGO
City: CHICAGO Country: UNITED STATES (US) INTERNAL MEDICINE/MEDICINE
SCHOOLS OF MEDICINE State Code: IL
District: 07
Other Information:
FOA: PA-19-056
Study Section: Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
Fiscal Year: 2020 Award Notice Date: 28-MAY-2020 DUNS Number: 005436803
Project Start Date: 1-JUN-2020
Budget Start Date: 1-JUN-2020 CFDA Code: 865
Project End Date: 28-FEB-2025
Budget End Date: 28-FEB-2021
Administering Institutes or Centers:
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
Project Funding Information for 2020:
Total Funding: $582,719
Direct Costs: $458,944
Indirect Costs: $123,775
Year Funding IC FY Total Cost by IC
2020 EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT $582,719
History:
Total project funding amount for 1 projects is $582,719*
* Only NIH,CDC,and FDA funding data.
Project Number Sub # Project Title Contact
Principal Investigator Organization FY Admin IC Funding IC FY Total Cost
by IC
1R01HD100630-01 AMH SIGNALING PATHWAY VARIATION IN PCOS URBANEK, MARGRIT NORTHWESTERN UNIVERSITY AT CHICAGO 2020 NICHD
NICHD $582,719
Subprojects:
Project Number Sub # Project Title Contact
Principal Investigator Organization FY Admin IC FY Total Cost
by IC
No Subprojects information available for 1R01HD100630-01
https://projectreporter.nih.gov/project_info_description.cfm?aid=9865636&icde=50955619
https://www.frontiersin.org/articles/10.3389/fendo.2020.00284/full
https://www.ncbi.nlm.nih.gov/pubmed/32670195?dopt=Abstract
Dietary flaxseed oil improved PCOS in rats, study finds
Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones-microbiota-inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.
Related Articles
Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones-Microbiota-Inflammation Axis in Rats.
Front Endocrinol (Lausanne). 2020;11:284
Authors: Wang T, Sha L, Li Y, Zhu L, Wang Z, Li K, Lu H, Bao T, Guo L, Zhang X, Wang H
Abstract
Polycystic ovary syndrome (PCOS) represents a common endocrine-metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague-Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-fed CON group (FO/CON), (c) PF with letrozole-induced PCOS model (MOD) group (PF/MOD), and (d) FO-fed MOD group (FO/MOD). All rats were fed a standard diet. After 3 weeks of modeling and subsequent 8 weeks of treatment, the rats in diverse groups were euthanized and associated indications were investigated. The results showed that dietary FO ameliorated the disorder of estrous cycle and ovarian morphology. In parallel, dietary FO improved the sex steroid hormone disturbance (luteinizing hormone/follicle-stimulating hormone, estrogen, testosterone, and progesterone), body weights, dyslipidemia, and insulin resistance. Moreover, FO treatment improved plasma and ovary inflammatory interleukin (IL)-1β, IL-6, IL-10, and IL-17A, tumor necrosis factor-α, and monocyte chemoattractant protein-1. Additionally, FO intervention significantly modulated the composition of gut microbiota and vaginal microbiota by increasing the abundances of Allobaculum, Lactobacillus, Butyrivibrio, Desulfovibrio, Bifidobacterium, Faecalibacterium, Parabacteroides as well as decreasing the abundances of Actinobacteria, Bacteroides, Proteobacteria, and Streptococcus, the ratio of Firmicutes/Bacteroidetes. A decrease in plasma lipopolysaccharide level and an increase in short-chain fatty acids, including acetic acid, propionic acid, butyric acid and pentanoic acid, were determined after dietary FO supplementation. Correlation analysis revealed close relationships among sex steroid hormones, inflammation, and gut/vaginal microbiota. Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones-microbiota-inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.
PMID: 32670195 [PubMed – in process]
https://clinicaltrials.gov/ct2/show/NCT03898934?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=03%2F19%2F2019&lupd_d=14
Condition : PCOS
Interventions : Drug: Vitamin D; Drug: Placebo Oral Tablet
Sponsor : Tanta University
Not yet recruiting
Vitamin D Supplementation in Lean PCOS Patients
NCT03898934
Tue, 02 Apr 2019 12:00:00 EDT
Last Update Posted: 04/02/19 08:08AM
https://clinicaltrials.gov/ct2/show/NCT03578497
Effects of IL-1 Receptor Antagonism on Testosterone Production in Women With Polycystic Ovary Syndrome (FertIL)
Anakinra
Kineret
Some new and interesting PCOS research that was added to the front page today (April 25, 2020):
Announcement: This site is still in development. Most recently, it was moved to faster and more reliable servers. Finally, the front page can “unpause” and resume updating several times per week again (as originally intended).
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231943
https://www.ncbi.nlm.nih.gov/pubmed/32330176?dopt=Abstract
Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study.
PLoS One. 2020;15(4):e0231943
Authors: Fouani FZ, Fadaei R, Moradi N, Zandieh Z, Ansaripour S, Yekaninejad MS, Vatannejad A, Mahmoudi M
Abstract
Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOS-RPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P <0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept. PMID: 32330176 [PubMed - as supplied by publisher]
https://www.sciencedirect.com/science/article/pii/S2451965020300399?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32676541?dopt=Abstract
Related Articles
Abnormal GnRH Pulsatility in Polycystic Ovary Syndrome: Recent Insights.
Curr Opin Endocr Metab Res. 2020 Jun;12:78-84
Authors: McCartney CR, Campbell RE
Abstract
Although the fundamental symptoms of polycystic ovary syndrome (PCOS) relate most directly to ovarian dysfunction, central neuroendocrine systems play a prominent role in its pathophysiology. Gonadotropin-releasing hormone (GnRH) pulse generator resistance to negative feedback contributes to rapid GnRH pulse secretion, which promotes gonadotropin abnormalities that foster ovarian hyperandrogenemia and ovulatory dysfunction. The causes of GnRH neuron dysfunction, however, have remained enigmatic. In this review, we highlight a number of recent preclinical and clinical studies pertinent to the neuroendocrine abnormalities of PCOS, including those that have provided important insights into the relevance of animal models with PCOS-like features, the potential roles of kisspeptin and γ-aminobutyric acid (GABA)-ergic neurons, and the potential role of anti-Müllerian hormone.
PMID: 32676541 [PubMed]
https://onlinelibrary.wiley.com/doi/abs/10.1111/cen.14198
https://www.ncbi.nlm.nih.gov/pubmed/32311120?dopt=Abstract
Association between polycystic ovary syndrome and the vaginal microbiome: a case-control study.
Clin Endocrinol (Oxf). 2020 Apr 20;:
Authors: Hong X, Qin P, Huang K, Ding X, Ma J, Xuan Y, Zhu X, Peng D, Wang B
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Some evidence suggests that dysbiosis of the gut microbiota could be associated with PCOS clinical parameters, but little is known for the association between vaginal microbiome and PCOS.
OBJECTIVE: To determine differences in the vaginal microbiome between women with PCOS and healthy control women.
RESEARCH DESIGN AND METHODS: In this case control study, the women with newly diagnosed PCOS (n = 39) and healthy controls (n = 40) were included from the hospital and maternal and child health center respectively. The vaginal swabs were collected, and microbiome structures were identified by 16S rRNA gene sequencing. The screening values for potential bacteria biomarker for PCOS were assessed by receiver operating characteristic curve (ROC) method.
RESULTS: There were significant difference in vaginal bacterial structures between PCOS and healthy control women. The vaginal bacterial species in the PCOS group were more diverse than the control group (Simpson index for PCOS group vs. control group: median 0.49 vs. 0.80, P = 0.008; Shannon index: median 1.07 vs. 0.44, P = 0.003; Chao1 index: median 85.12 vs. 66.13, P < 0.001). The relative abundance of Lactobacillus crispatus in the PCOS group was significant lower than controls (P = 0.001), and the relative abundance of Mycoplasma and Prevotella were higher than controls (P < 0.001, P = 0.002, respectively). The Mycoplasma genus could be a potential biomarker for PCOS screening, as ROC analysis showed that the area under the curve (AUC) for the relative abundance of Mycoplasma was 0.958 (95% CI: 0.901-0.999). Subgroup analyses also showed these associations would not change among the women with the same BMI level and vagina cleanliness grading. CONCLUSIONS: In the vaginal microbiome, the Mycoplasma genus was associated with PCOS. Further research is required to explore causal correlations between PCOS and the vaginal microbiome. PMID: 32311120 [PubMed - as supplied by publisher]
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-020-00919-5
Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials
https://projectreporter.nih.gov/project_info_description.cfm?aid=9916787&icde=50955619
Parent Project Number: 5P50HD012303-38 Sub-Project ID: 7801 Contact PI / Project Leader: CHANG, R JEFFREY
Title: THE ROLE OF ANDROGEN ON FOLLICLE FUNCTION Awardee Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Abstract Text:
PROJECT SUMMARY In women with polycystic ovary syndrome (PCOS) androgen excess is fundamental to the clinical and physiological alterations of this disorder. In particular, androgen overproduction induces distinctive PCO morphology and appears to influence follicle function. Studies conducted in animals and nonhuman primates have demonstrated that androgens increase follicle number and in small antral follicles enhance granulosa cell (GC) responsiveness to gonadotropin stimulation. However, androgens also have been shown to clearly inhibit GC aromatase activity, and in PCOS follicular fluid, androgen content is abnormally increased. Efforts to reconcile these differences are nonexistent. Moreover, appropriate clinical studies to examine the effects of androgen on follicle health in women are lacking. Excessive androgen exposure in women due to functional tumors or high-dose testosterone treatment in F-M transsexuals has been associated with PCO morphology. Use of androgen therapy to promote follicle growth prior to ovarian hyperstimulation in women undergoing in vitro fertilization has not provided consistent results. However, in these studies GC responses to FSH were not carefully assessed, study populations were exclusively women with previously poor ovarian responses to FSH, and women with PCOS were not included. In fact, there are essentially no clinical studies that have addressed in detail the impact of androgen on follicle function in normal or PCOS women. We hypothesize that androgen facilitates GC responses to FSH in normal women and androgen excess further amplifies follicle growth and function in women with PCOS. In Aim 1, we propose to study the effect of increased ovarian androgen on follicle function by increasing intraovarian androgen accumulation using aromatase inhibition followed by FSH stimulation. In Aim 2, we will examine potential mechanisms of androgen-follicle interaction in PCOS as 17- hydroxyprogesterone and androgen responses to hCG stimulation are highly variable and in some women overlap with those of normal controls. These studies will include association with follicle cohort size, effect of hyperinsulinemia, and impact of hyperandrogenemia by assessment of follicle stimulation after long-term androgen suppression. These clinical studies will be complemented by investigation of the intrafollicular, paracrine relationship between excess TC androgen production and GC factors in Aim 3, in which we will create transgenic mice overexpressing Cyp17 in TCs and determine the effects on ovarian morphology, folliculogenesis and fertility. These studies will also examine paracrine mechanisms that may associate with androgen excess in cultured follicles. The experiments in this project are designed to provide insight into whether androgen excess facilitates or interferes with follicle function and ovulation in women with PCOS.
Project Terms:
Address; Agonist; Androgen Suppression; Androgen Therapy; Androgens; Animal Model; Animals; Antral; Aromatase; Aromatase Inhibition; base; Cell Communication; Cetrorelix; Clinical; Clinical Research; cohort; Complement; design; Diazoxide; Disease; Dose; Exhibits; experimental study; Exposure to; Fertility; Fertilization in Vitro; Follicular Fluid; folliculogenesis; GNRH1 gene; Gonadotropin Releasing Hormone Inhibitor; Gonadotropins; granulosa cell; Growth; Growth and Development function; Health; Human Chorionic Gonadotropin; Hydroxyprogesterone; Hyperinsulinism; Hyperplasia; In Vitro; in vivo; Injections; insight; Insulin; Intention; intraovarian; Investigation; Letrozole; Medicine; Methods; Morphology; mouse model; mullerian-inhibiting hormone; Mus; nonhuman primate; Ovarian; Ovarian Ablation; Ovarian Hyperstimulation Syndrome; overexpression; Ovulation; paracrine; Physiological; Polycystic Ovary Syndrome; Production; recombinase-mediated cassette exchange; reproductive; response; Role; Science; Spironolactone; study population; System; Testing; Testosterone; Tetracyclines; theca cell; Transgenic Mice; transsexual; tumor; Woman
Contact PI Information: Program Official Information: Other PI Information:
Name: CHANG, R JEFFREY
Email: Click to view contact PI email address
Title: Name: Unavailable Not Applicable
Organization: Department / Educational Institution Type: Congressional District:
Name: UNIVERSITY OF CALIFORNIA, SAN DIEGO
City: LA JOLLA Country: UNITED STATES (US) Unavailable
Unavailable State Code: CA
District: 52
Other Information:
FOA: RFA-HD-16-010
Study Section: Special Emphasis Panel (ZHD1-DRG-S)
Fiscal Year: 2020 Award Notice Date: 1-APR-2020 DUNS Number: 804355790
Project Start Date:
Budget Start Date: 1-APR-2020 CFDA Code:
Project End Date:
Budget End Date: 31-MAR-2021
Administering Institutes or Centers:
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
Project Funding Information for 2020:
Total Funding: $439,504
Direct Costs: $284,860
Indirect Costs: $154,644
Year Funding IC FY Total Cost by IC
2020 $439,504
https://onlinelibrary.wiley.com/doi/abs/10.1002/cbin.11349
https://www.ncbi.nlm.nih.gov/pubmed/32222120?dopt=Abstract
Related Articles
Long Non-coding RNA NEAT1 Drives the Development of Polycystic Ovary Syndrome via Sponging Multiple MicroRNAs.
Cell Biol Int. 2020 Mar 28;:
Authors: Sang X, Zhang Y
Abstract
A line of evidences have validated that multiple microRNAs (including miR-16, miR-483 and miR-324-3p) were abnormally expressed in granulosa cells, which may be closely related with the pathogenesis of polycystic ovary syndrome (PCOS). Long-chain non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been proved to participate in the progression of various human diseases via regulating microRNAs, but its function in PCOS are not yet clear. In this work, RT-PCR was performed to detect NEAT1 expression in PCOS tissues, and human ovarian granulosa cell line KGN were taken as the model to construct the cell line with high expression and low expression of NEAT1. CCK-8 and flow cytometry were carried out to monitor cells proliferation and apoptosis, respectively. Besides, we performed luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay to verify the interaction between NEAT1, miR-16, miR-483 and miR-324-3p. We demonstrated that NEAT1 was highly expressed in PCOS tissues and cells. Over-expressed NEAT1 promoted the proliferation and inhibited the apoptosis. Moreover, NEAT1 was negatively correlated with the expression levels of miR-16, miR-483 and miR-324-3p. Dual luciferase analysis and RIP assay confirmed that NEAT1 can specifically bind to miR-16, miR-483 and miR-324-3p, by which NEAT1 can reduce their expression. In conclusion, NEAT1 can promote the proliferation of ovarian granulosa cells and arrest apoptosis via impeding expressions of miR-16, miR-483 and miR-324-3p. Our research would shed new light on the molecular mechanism of ovarian granulosa cell disorder. This article is protected by copyright. All rights reserved.
PMID: 32222120 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03717935?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=04%2F04%2F2019&lupd_d=14
Conditions : Polycystic Ovarian Syndrome; Obesity; Hepatic Steatosis
Interventions : Dietary Supplement: Essential Amino Acid (EAA) Supplement; Other: Placebo
Sponsor : University of Colorado, Denver
Recruiting
Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
NCT03717935
Wed, 24 Oct 2018 12:00:00 EDT
Last Update Posted: 04/18/19 08:12AM
https://www.sciencedirect.com/science/article/abs/pii/S0378874119350159?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32151755?dopt=Abstract
Related Articles
Effects of cinnamon on controlling metabolic parameters of polycystic ovary syndrome: A systematic review and meta-analysis.
J Ethnopharmacol. 2020 Mar 06;:112741
Authors: Heydarpour F, Hemati N, Hadi A, Moradi S, Mohammadi E, Farzaei MH
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamon as a traditional medicine has been widely used in various disorders such as headache, toothache, common cold, diarrhea, flatulence, fever, amenorrhea frigidity. However, the effect of cinnamon supplementation on metabolic parameters of polycystic ovary syndrome (PCOS) patients has not been fully assessed.
AIM OF THE STUDY: Clinical trials have shown contradictory effects of cinnamon supplementation on metabolic parameters of polycystic PCOS patients. Therefore, we evaluated the effect of cinnamon supplementation on metabolic parameters of PCOS patients through a systematic review and meta-analysis of clinical trials.
MATERIALS AND METHODS: PubMed, Embase, the Cochrane library, Scopus and Web of Science databases (until August 2019) were searched to identify potential clinical trials with information on cinnamon supplementation on metabolic parameters among PCOS patients. Weighted Mean Differences was pooled using a random-effects model. Standard methods were used for assessment of heterogeneity, publication bias and sensitivity analysis.
RESULTS: Pooling five clinical trials (five treatment arms) together did not show any significant effect on body weight (WMD: -0.74 kg, 95% CI: -3.17 to 1.69) and body mass index (BMI) (WMD: -1.47, 95% CI: -4.07 to 1.12). Our results illustrated that a significant decrease of fasting blood sugar (WMD: -5.32, mg/dL95% CI: -10.46 to -0.17), fasting insulin (WMD: -4.10, μIU/dL95% CI: -6.76 to -0.144) and HOMA-IR (WMD: -0.69 95% CI: -1.37 to -0.004) were observed after cinnamon treatment. Moreover, our findings demonstrated that oral cinnamon supplementation in PCOS patients led to significant reduction of serum level of LDL-C, total cholesterol, and triacylglycerol. Besides, an improvement of serum concentration of HDL-C was shown by cinnamon supplementation.
CONCLUSION: Generally, present study indicated that cinnamon supplementation may help PCOS patients to manage their metabolic parameters. Future prospective randomized clinical trials with longer intervention duration are warranted to obtain a precise conclusion.
PMID: 32151755 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03778099
The Effect of Cinnamon on Ovulation Induction in Women With Polycystic Ovary Syndrome (PCOS)
https://www.spandidos-publications.com/10.3892/ijmm.2020.4522
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138261/
https://www.ncbi.nlm.nih.gov/pubmed/32323743?dopt=Abstract
Proteomics analysis of potential serum biomarkers for insulin resistance in patients with polycystic ovary syndrome.
Int J Mol Med. 2020 Mar 03;:
Authors: Li L, Zhang J, Zeng J, Liao B, Peng X, Li T, Li J, Tan Q, Li X, Yang Y, Chen Z, Liang Z
Abstract
The aim of the present study was to identify potential serum biomarkers for insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS) by comparing the differences in serum protein expression levels between PCOS patients with and without IR. PCOS patients aged from 18 to 35 years were recruited at Guangdong Women and Children’s Hospital from January, 2013 to February, 2014. A total of 218 PCOS patients were enrolled and divided into the insulin resistance (PCOS‑IR) and non‑insulin resistance (PCOS‑NIR) groups according to their homeostasis model assessment of insulin resistance. Two‑dimensional difference gel electrophoresis (2D‑DIGE) and matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF‑MS/MS) techniques were used to identify differences in protein expression levels between the PCOS‑IR and PCOS‑NIR groups. The present study demonstrated that the total cholesterol (TCH), triglycerides (TG), low‑density lipoprotein (LDL), fasting plasma glucose (FPG), 3‑h blood glucose (3hBG) and uric acid (UA) levels in the PCOS‑IR group were higher than those in the PCOS‑NIR group (P<0.05). Between the PCOS‑IR and PCOS‑NIR groups, a total of 20 differentially expressed protein spots were detected by 2D‑DIGE. Among these, 4 proteins, namely afamin, serotransferrin, complement C3 and apolipoprotein C3 (APOC3), were also identified by MALDI‑TOF‑MS/MS. The alteration of APOC3 was further confirmed by western blot analysis and enzyme‑linked immunosorbent assay (ELISA). The present study also confirmed that the expression level of APOC3 was positively associated with the homeostasis model assessment of insulin resistance (HOMA‑IR). On the whole, the data indicate that APOC3 may be a potential diagnostic marker for PCOS‑IR patients. PMID: 32323743 [PubMed - as supplied by publisher]
https://pubmed.ncbi.nlm.nih.gov/32103756-effects-of-a-ketogenic-diet-in-overweight-women-with-polycystic-ovary-syndrome/?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pubmed/32103756?dopt=Abstract
Effects of a ketogenic diet in overweight women with polycystic ovary syndrome.
J Transl Med. 2020 Feb 27;18(1):104
Authors: Paoli A, Mancin L, Giacona MC, Bianco A, Caprio M
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterised clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. It is associated with an increased prevalence of metabolic syndrome, cardiovascular disease and type 2 diabetes. The onset of PCOS has been associated to several hereditary and environmental factors, but insulin resistance plays a key pathogenetic role. We sought to investigate the effects of a ketogenic diet (KD) on women of childbearing age with a diagnosis of PCOS.
METHODS: Fourteen overweight women with diagnosis of PCOS underwent to a ketogenic Mediterranean diet with phyoextracts (KEMEPHY) for 12 week. Changes in body weight, body mass index (BMI), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), insulin, glucose, HOMA-IR, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TGs), total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH); dehydroepiandrosterone sulfate (DHEAs), estradiol, progesterone, sex hormone binding globulin (SHBG) and Ferriman Gallwey score were evaluated.
RESULTS: After 12 weeks, anthropometric and body composition measurements revealed a significant reduction of body weight (- 9.43 kg), BMI (- 3.35), FBM (8.29 kg) and VAT. There was a significant, slightly decrease of LBM. A significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of HOMA-IR. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced.
CONCLUSIONS: Our results suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS. Trial registration Clinicaltrial.gov, NCT04163120, registrered 10 November 2019, retrospectively registered, https://clinicaltrials.gov.
PMID: 32103756 [PubMed – in process]
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-020-00905-x
https://www.ncbi.nlm.nih.gov/pubmed/32106860?dopt=Abstract
Related Articles
Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study.
BMC Womens Health. 2020 Feb 27;20(1):39
Authors: Li L, Zhang R, Zeng J, Ke H, Peng X, Huang L, Zhang H, Chen Z, Li TT, Tan Q, Yang Y, Li X, Li X
Abstract
BACKGROUND: To investigate the effectiveness and safety of 3 mg drospirenone and 20 μg ethinyl estradiol tablet (3 mg DRSP/20 μg EE) in the treatment of polycystic ovary syndrome (PCOS).
METHODS: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 μg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated.
RESULTS: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. CONCLUSIONS: Treatment of PCOS patients with3 mg DRSP/20 μg EE has shown beneficial hormonal and lipid profile along with considerable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022001, March 2019, retrospectively registered. PMID: 32106860 [PubMed - in process]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078124/
https://www.ncbi.nlm.nih.gov/pubmed/32179451?dopt=Abstract
https://www.cell.com/molecular-therapy-family/nucleic-acids/pdf/S2162-2531(20)30079-2.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253120300792%3Fshowall%3Dtrue
Inhibited PVT1 and overexpressed miR-17-5p result in downregulation of PTEN and promotion of cell proliferation, as well as inhibition of apoptosis of ovarian granulosa cells in PCOS
lncRNA PVT1/MicroRNA-17-5p/PTEN Axis Regulates Secretion of E2 and P4, Proliferation, and Apoptosis of Ovarian Granulosa Cells in PCOS.
Mol Ther Nucleic Acids. 2020 Feb 13;20:205-216
Authors: Liu G, Liu S, Xing G, Wang F
Abstract
Recently, the roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were identified in polycystic ovary syndrome (PCOS). In the present study, we investigated the role of the lncRNA PVT1/miR-17-5p/PTEN axis in PCOS ovarian granulosa cells. Expression of PVT1, miR-17-5p and PTEN in PCOS ovarian granulosa cells and follicular fluid was detected, and homeostatic model assessment of insulin resistance (HOMA-IR) and the levels of fasting plasma glucose (FPG), fasting insulin (FINS), and sex hormones were assessed. Then, the proliferation, apoptosis, and colony formation ability of ovarian granulosa cells were evaluated. The binding relationship between PVT1 and miR-17-5p as well as the target relationship between miR-17-5p and PTEN were determined by bioinformatics analysis, luciferase activity assay, RNA-induced silencing complex assay, and RNA pull-down assay. The levels of sex hormone-binding globulin and follicle-stimulating hormone were abated and the levels of luteinizing hormone, testosterone, FINS, FPG, and HOMA-IR were increased in PCOS serum. PVT1 and PTEN were overexpressed and miR-17-5p was reduced in PCOS ovarian granulosa cells and follicular fluid. Overexpressed miR-17-5p and inhibited PVT1 could decelerate apoptosis while accelerating colony formation ability and proliferation of ovarian granulosa cells in PCOS. Moreover, overexpression of PVT1 and reduced miR-17-5p could reverse these results. There existed target relation among PVT1, miR-17-5p, and PTEN, and PVT1 could inhibit miR-17-5p, thereby elevating PTEN. Our study suggests that inhibited PVT1 and overexpressed miR-17-5p result in downregulation of PTEN and promotion of cell proliferation, as well as inhibition of apoptosis of ovarian granulosa cells in PCOS.
PMID: 32179451 [PubMed – as supplied by publisher]
https://www.sciencedirect.com/science/article/pii/S221287782030003X
https://www.ncbi.nlm.nih.gov/pubmed/32244180?dopt=Abstract
Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies.
Mol Metab. 2020 Feb 05;35:100937
Authors: Sanchez-Garrido MA, Tena-Sempere M
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome’s metabolic complications remain limited.
SCOPE OF REVIEW: This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions.
MAJOR CONCLUSIONS: Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.
PMID: 32244180 [PubMed – as supplied by publisher]
https://www.biospace.com/article/releases/evotec-and-bayer-announce-new-alliance-focusing-on-drug-discovery-for-polycystic-ovary-syndrome-with-novel-targets-from-celmatix-/
Evotec and Bayer Announce New Alliance Focusing on Drug Discovery for Polycystic Ovary Syndrome With Novel Targets From Celmatix
https://www.birmingham.ac.uk/news/latest/2019/12/polycystic-ovary-syndrome-treatment-research.aspx
Major research project aims to improve treatment for women with polycystic ovary syndrome
A major £2.4 million research project is underway at the University of Birmingham aimed at improving treatment for women with polycystic ovary syndrome (PCOS).
https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/dez205/5670381
Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome
A Romero-Ruiz, K Skorupskaite, F Gaytan, E Torres, C Perdices-Lopez, B M Mannaerts, S Qi, S Leon, M Manfredi-Lozano, C Lopez-Rodriguez … Show more
Human Reproduction, dez205, https://doi.org/10.1093/humrep/dez205
Published: 10 December 2019 Article history
Received: 05 April 2019
Revision received: 25 August 2019
Revision requested: 03 September 2019
Published: 10 December 2019
https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/EP088147
https://www.ncbi.nlm.nih.gov/pubmed/31803965?dopt=Abstract
Hydroxysafflor yellow A exerts beneficial effects via restoring hormone secretion and alleviating oxidative stress in polycystic ovary syndrome mice.
Exp Physiol. 2019 Dec 05;:
Authors: Luo M, Huang JC, Yang ZQ, Wang YS, Guo B, Yue ZP
Abstract
NEW FINDINGS: What is the central question of this study? The aim of this study was to evaluate the potential therapeutic role of Ginsenoside Rb1 and HSYA in PCOS. What is the main finding and its importance? The main finding is that HSYA restored the estrous cycles of PCOS mice, reduced follicular cysts in ovaries and rescued the abnormal hormone secretion, while Ginsenoside Rb1 did not ameliorate the main symptoms of PCOS mice. Meanwhile, HSYA alleviated oxidative stress along with the enhancement of antioxidant enzyme activities. These evidences highlight a potential role of HSYA in PCOS therapy.
ABSTRACT: Polycystic ovary syndrome (PCOS) is the most common endocrine disease resulted in woman infertility. Hydroxysafflor yellow A (HSYA) and Ginsenoside Rb1 are shown to have antioxidant properties, but little is known about their impact in PCOS. Here DHEA was used to induce PCOS mouse model which was characterized by irregular estrous cycle, cystic follicles and elevated serum T level. Supplementation of HSYA restored the estrous cycle of PCOS mice and reduced follicular cysts in PCOS mice ovaries along with the decline in serum T level, while Ginsenoside Rb1 did not ameliorate above symptoms of PCOS mice. Meanwhile, after HSYA treatment, elevation of serum E2 , P4 , LH and AMH levels as well as reduction of FSH level exhibited the obvious improvement, but Ginsenoside Rb1 only rescued the levels of FSH and AMH. Further analysis evidenced that HSYA reversed the expression of steroid hormone secretion-related genes Star, Hsd3b1, Cyp11a1 and Cyp19a1. In PCOS mice, HSYA weakened the elevation of ovarian MDA which was regarded as the biomarker for oxidative stress. Moreover, HSYA improved GSH content accompanying with a simultaneous increase in GSH/GSSG ratio and enhanced the activities of antioxidant enzymes SOD, GSH-Px and CAT. Collectively, HSYA exerted beneficial effects on PCOS mice via restoring hormone secretion and alleviating oxidative stress. This article is protected by copyright. All rights reserved.
PMID: 31803965 [PubMed – as supplied by publisher]
https://www.sciencedirect.com/science/article/pii/S0003426619302161?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32127169
https://www.ncbi.nlm.nih.gov/pubmed/32127169?dopt=Abstract
Related Articles
Several critical genes and microRNAs associated with the development of polycystic ovary syndrome.
Ann Endocrinol (Paris). 2019 Nov 11;:
Authors: Wang W, Ji J, Li J, Ren Q, Gu J, Zhao Y, Hong D, Guo Q, Tan Y
Abstract
BACKGROUND: We aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS).
METHODS: GSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein-protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated.
RESULTS: Spleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3’UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway.
CONCLUSIONS: Our results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS.
PMID: 32127169 [PubMed – as supplied by publisher]
https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1025-3711
https://www.ncbi.nlm.nih.gov/pubmed/31683329?dopt=Abstract
Several Circulating Biomarkers for PCOS Diagnosis.
Exp Clin Endocrinol Diabetes. 2019 Nov 04;:
Authors: Luo P, Zhang C, He Y, Yang G, Liu H, Li L
Abstract
AIMS: Irisin, Betatrophin and Zinc-α2-glycoprotein (ZAG) have been shown to be associated with insulin resistance (IR) and polycystic ovary syndrome (PCOS), respectively. The purpose of this study is to explore the potential accuracy of this combination of three cytokines in screening PCOS.
METHODS: 186 individuals were recruited for this study. Circulating Irisin, Betatrophin and ZAG concentrations were measured by enzyme-linked immunosorbent assay. The association between these serum biomarkers and PCOS was assessed by logistic regression analysis. Receiver operating curve (ROC) analysis was performed to evaluate the diagnostic value of these biomarkers for PCOS women.
RESULTS: In women with PCOS, serum Irisin and Betatrophin levels were markedly elevated compared to those in healthy controls (p<0.01), while ZAG levels were lower (p<0.01). PCOS women with IR (M-value<6.28) had lower circulating ZAG concentrations, and higher circulating Irisin and Betatrophin levels relative to PCOS women without IR (M-value ≥ 6.28). ROC curve analyses showed that the AUC for Irisin, ZAG and Betatrophin for predicting PCOS were 0.77, 0.83 and 0.85, respectively. In a joint ROC curves analysis of these serum markers and other parameters, the results showed that the AUC was 0.93, and the sensitivity and specificity were 82.1 % and 92.3 %, respectively. CONCLUSIONS: When compared to using single cytokine, the analysis of Irisin, ZAG and Betatrophin elevates the accuracy in diagnosing PCOS. PMID: 31683329 [PubMed - as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03229408?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=10%2F18%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Drug: Salsalate; Other: Placebo
Sponsors : University of Illinois at Chicago; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruiting
Treating Inflammation in Polycystic Ovary Syndrome to Ameliorate Ovarian Dysfunction
NCT03229408
Tue, 25 Jul 2017 12:00:00 EDT
Last Update Posted: 11/01/19 07:36AM
https://clinicaltrials.gov/ct2/show/NCT03843736?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=02%2F04%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Behavioral: Lifestyle intervention; Drug: Probiotic Agent; Drug: Oral contraceptive
Sponsors : Peking Union Medical College Hospital; Peking Union Medical College
Not yet recruiting
The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.
NCT03843736
Mon, 18 Feb 2019 12:00:00 EST
Last Update Posted: 02/18/19 10:26AM
https://finance.yahoo.com/news/evotec-celmatix-enter-strategic-collaboration-055000478.html
Evotec And Celmatix Enter Into Strategic Collaboration
TO DEVELOP NOVEL PRE-CLINICAL PROGRAMMES FOR HIGH UNMET MEDICAL NEED CONDITIONS FOR WOMEN
Evotec and Celmatix enter into strategic collaboration to develop novel pre-clinical programmes for underserved conditions affecting women’s reproductive health, including polycystic ovary syndrome (PCOS), endometriosis, and infertility
https://clinicaltrials.gov/ct2/show/NCT04120597?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=09%2F25%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Drug: Zishen Qingre Lishi Huayu Granules; Drug: Placebo
Sponsor : Jiangxi University of Traditional Chinese Medicine
Zishen Qingre Lishi Huayu Recipe restores spontaneous ovulation in PCOS patients
Zishen Qingre Lishi Huayu Granules
Not yet recruiting
Clinical and Basic Research on the Treatment of Polycystic Ovary Syndrome
NCT04120597
Wed, 09 Oct 2019 12:00:00 EDT
Last Update Posted: 10/09/19 10:45AM
https://www.ncbi.nlm.nih.gov/pubmed/31580245?dopt=Abstract
http://www.eurekaselect.com/175312/article
Epigenetic marks in Polycystic Ovary Syndrome.
Curr Med Chem. 2019 Oct 03;:
Authors: Motta AB
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects women in their reproductive age. Recent studies have shown that genes have an important role in the etiology of PCOS. However, the precise way in which these genes are transcriptionally and post-transcriptionally regulated is poorly understood. The aim of the present review is to provide updated information on miRNAs and DNA methylation as epigenetic marks of PCOS. The data presented here allow concluding that both microRNAs and DNA methylation can be considered as possible useful biomarkers when choosing the treatment for a specific PCOS phenotype and thus represent two important tools for the diagnosis and treatment of PCOS patients.
PMID: 31580245 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03493984?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=09%2F13%2F2019&lupd_d=14
A Preliminary Clinical Trial Investigating the Ability of Plant Exosomes to Mitigate Insulin Resistance and Chronic Inflammation in Patients Diagnosed With Polycystic Ovary Syndrome (PCOS)
Condition : Polycystic Ovary Syndrome
Interventions : Other: Ginger exosomes; Other: Aloe exosomes; Other: Placebo
Sponsor : University of Louisville
Recruiting
Plant Exosomes and Patients Diagnosed With Polycystic Ovary Syndrome (PCOS) 17
NCT03493984
Wed, 11 Apr 2018 12:00:00 EDT
Last Update Posted: 09/27/19 07:07AM
https://clinicaltrials.gov/ct2/show/NCT03578497?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=09%2F04%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Intervention : Drug: IL-1 receptor antagonist Anakinra
Sponsor : University Hospital, Basel, Switzerland
Recruiting
Effects of IL-1 Receptor Antagonism on Testosterone Production in Women With Polycystic Ovary Syndrome
NCT03578497
Fri, 06 Jul 2018 12:00:00 EDT
Last Update Posted: 09/18/19 07:52AM
https://www.tandfonline.com/doi/full/10.1080/21691401.2019.1669619
https://www.ncbi.nlm.nih.gov/pubmed/31549864?dopt=Abstract
Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS).
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3804-3813
Authors: Zhao Y, Tao M, Wei M, Du S, Wang H, Wang X
Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive disease. Adipose mesenchymal stem cells (AMSCs) can produce a mass of exosomes. The objective of this study was to determine the effects of exosomal miR-323-3p on cumulus cells (CCs) of PCOS patients. Exosomal miR-323-3p were collected from modified AMSCs. Real-time PCR, western blots, MTT assays, flow cytometry, luciferase reporter assays and a letrozole-induced PCOS mouse model were used to identify mechanisms of exosomal miR-323-3p on CCs. The results revealed that miR-323-3p expression was upregulated in AMSCs, exosomes and CCs. Upregulated miR-323-3p promoted cell proliferation and suppressed apoptosis in CCs, while miR-323-3p inhibitor exerted opposite roles in exosome-treated CCs. Moreover, PDCD4 was upregulated in PCOS CCs, displayed an inverse expression pattern to those of miR-323-3p, and was a direct target of miR-323-3p. Overexpression of PDCD4 reversed the effects of upregulated miR-323-3p on CCs. Serum FSH, LH and testosterone were upregulated while E2 levels were downregulated in the PCOS mice. Upregulation of miR-323-3p alleviated PCOS by suppressing CCs’ apoptosis through targeting PDCD4 in vivo. The results demonstrated that exosomal miR-323-3p promoted cell proliferation and inhibited apoptosis in CCs through targeting PDCD4 in PCOS. This study provides insight into developing new therapeutic strategies for PCOS.
PMID: 31549864 [PubMed – in process]
https://www.europeanreview.org/article/18823
https://www.ncbi.nlm.nih.gov/pubmed/31539108?dopt=Abstract
MicroRNA-486-5p can bind to MST4 in a targeted manner and inhibit the proliferation of ovarian granulosa cells, thereby inhibiting the development of PCOS
MicroRNA-486-5p inhibits ovarian granulosa cell proliferation and participates in the development of PCOS via targeting MST4.
Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7217-7223
Authors: Han XM, Tian PY, Zhang JL
Abstract
OBJECTIVE: To explore whether microRNA-486-5p affected the proliferation of ovarian granulosa cells by targeting MST4 (silk/threonine protein kinase 4), thereby promoting the development of polycystic ovary syndrome (PCOS).
MATERIALS AND METHODS: The level of microRNA-486-5p in PCOS tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After microRNA-486-5p up-regulation in KNG cells, the mRNA and protein level of related genes was examined using qRT-PCR and western blot assay, respectively. Meanwhile, cell proliferation and cell cycle were analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. After insulin treatment of KNG cells, expressions of microRNA-486-5p and MST4, cell proliferation as well as cell cycle, were detected by qRT-PCR, CCK-8 and flow cytometry, respectively. Furthermore, cell proliferation and cycle situation were examined after simultaneous up-regulation of MST4 and microRNA-486-5p in vitro.
RESULTS: MicroRNA-486-5p expression in PCOS tissues was significantly lower than that of normal tissues. In KNG cells, up-regulation of microRNA-486-5p significantly inhibited cell proliferation and cell cycle. The levels of cycle-associated proteins including CDK2 and CCNB1 decreased significantly. The results of dual-luciferase reporter gene assay showed that microRNA-486-5p could bind to MST4. After up-regulating microRNA-486-5p, both the mRNA and protein levels of MST4 decreased remarkably. MST4 expression was found significantly elevated in PCOS tissues as well. After overexpression of MST4, cell proliferation was enhanced, cell cycle was promoted, and expressions of cycle-related proteins increased. After treatment with different concentrations of insulin in KNG cells, the expression level of microRNA-486-5p decreased in a concentration-dependent manner. However, opposite results were observed in MST4 level. Meanwhile, the proliferation ability and cell cycle of insulin-treated cells were significantly enhanced. In addition, the inhibitory effect of microRNA-486-5p on cell proliferation and cell cycle could be partially reversed by simultaneous up-regulation of MST4 and microRNA-486-5p.
CONCLUSIONS: MicroRNA-486-5p can bind to MST4 in a targeted manner and inhibit the proliferation of ovarian granulosa cells, thereby inhibiting the development of PCOS.
PMID: 31539108 [PubMed – in process]
New Research Suggests Probiotics Could Play A Part In The Treatment Of PCOS
New Research Suggests Probiotics Could Play A Part In The Treatment Of PCOS
https://academic.oup.com/jes/article/3/12/2204/5569849
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839531/
Colocalization of Polycystic Ovary Syndrome Candidate Gene Products in Theca Cells Suggests Novel Signaling Pathways
Rewa Kulkarni, Maria E Teves, Angela X Han, Jan M McAllister, Jerome F Strauss, III Author Notes
Journal of the Endocrine Society, Volume 3, Issue 12, December 2019, Pages 2204–2223, https://doi.org/10.1210/js.2019-00169
Published: 16 September 2019 Article history
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Abstract
Genome-wide association studies identified loci associated with polycystic ovary syndrome (PCOS), including those near the LH receptor gene (LHCGR), a clathrin-binding protein (DENND1A) that functions as a guanine nucleotide exchange factor, and the gene encoding RAB5B, a GTPase involved in vesicular trafficking. We proposed that these three PCOS loci could be assembled into a functional network that contributes to altered gene expression in theca cells, resulting in increased androgen synthesis. The functional significance of this network was supported by our discovery that a truncated protein splice variant of the DENND1A gene, termed DENND1A.V2, is elevated in PCOS theca cells, and that forced expression of DENND1A.V2 in normal theca cells increased CYP11A1 and CYP17A1 expression and androgen synthesis, a hallmark of PCOS. In this study, we demonstrate the colocalization of LHCGR, DENND1AV.2, and RAB5B proteins in various cellular compartments in normal and PCOS theca cells by immunofluorescence. Human chorionic gonadotropin and forskolin stimulation was shown to affect the cytoplasmic distribution of LHCGR, DENND1A.V2, and RAB5B. DENND1A.V2 accumulated in the nuclei of the theca cells. Moreover, PCOS theca cells, following forskolin treatment, had a significantly greater relative abundance of nuclear DENND1A.V2. RAB5B also accumulated in the nuclei of PCOS theca cells treated with forskolin. In contrast, LHCGR did not enter the nucleus. This cytological evidence, and the previously reported increase in androgen biosynthesis with forced expression of DENND1A.V2 in normal theca cells, raises the possibility that DENND1A.V2 and RAB5B participate in increasing transcription of genes involved in androgen synthesis.
https://academic.oup.com/jcem/article-abstract/105/1/136/5569914?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/31529097?dopt=Abstract
Related Articles
Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome.
J Clin Endocrinol Metab. 2020 01 01;105(1):
Authors: Devin JK, Nian H, Celedonio JE, Wright P, Brown NJ
Abstract
CONTEXT: Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion.
OBJECTIVE: We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS.
METHODS: Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm.
RESULTS: During OGTT, sitagliptin increased glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean -17.2 mg/dL [95% CI, -27.7 to -6.6]; P < 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P < 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo). CONCLUSIONS: Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. CLINICAL TRIAL REGISTRATION: This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant. PMID: 31529097 [PubMed - indexed for MEDLINE]
https://www.globenewswire.com/news-release/2019/09/11/1914094/0/en/BioRestorative-Therapies-Announces-New-Initiative-to-Target-Polycystic-Ovarian-Syndrome.html
BioRestorative Therapies Announces New Initiative to Target Polycystic Ovarian Syndrome
https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0554-9
https://www.ncbi.nlm.nih.gov/pubmed/31470879?dopt=Abstract
Related Articles
Effect of phlebotomy versus oral contraceptives containing cyproterone acetate on the clinical and biochemical parameters in women with polycystic ovary syndrome: a randomized controlled trial.
J Ovarian Res. 2019 Aug 30;12(1):78
Authors: Behboudi-Gandevani S, Abtahi H, Saadat N, Tohidi M, Ramezani Tehrani F
Abstract
BACKGROUND: Reduction of the body iron stores can improve hyperandrogenemia and insulin resistance. This study aimed to compare clinical and para-clinical responses to the treatment of phlebotomy using oral contraceptive pills (OCs) containing cyproterone acetate in women with PCOS.
METHODS: In this randomized clinical trial, 64 patients with PCOS were randomly assigned to the phlebotomy and OCs groups (n = 32 in each group). The intervention group, using a single treatment procedure, underwent venesection of 450 mL of whole blood at the early follicular phase of the spontaneous or progesterone-induced menstrual cycle. The control group received OCs pills for 3 months from the 1th day of spontaneous or progesterone-induced menstrual cycle onwards for 3 weeks, followed by a pill-free interval of 7 days. The women were evaluated after the 3-month intervention. The primary outcome measure was a change in the HOMA-IR and free androgen index (FAI). Secondary outcomes were changes in the Ferriman-Gallwey (FG) score and other clinical, biochemical and hormonal changes from the baseline (pre-treatment) to week 12.
RESULTS: In the phlebotomy group, 27 (84.3%) and in the OCs group 30 (93.7%) of the women completed the 3-month follow-up. The median HOMA-IR significantly decreased from 3.5 to 2.7 in the phlebotomy, and from 3.1 to 2.8 in the OCs group, and the changes were comparable between the groups. Median changes in the FAI significantly decreased in both groups, but the differences were not statistically significant between the groups (P = 0.061). With regard to secondary outcomes, mean FG scores in both groups significantly decreased [from 16.8 (6) to 13.3 (7.4), P < 0.028] in the phlebotomy group and [from 14.3 (7) to 9.8 (7.6) in the OCs group, P = 0.001] after 3 months of treatment, but such changes had no statistically significant differences between the groups. During treatment, menstrual cycles became regular in all women in the OCs group and in 12.27 (44.4%) of the women in the phlebotomy group, and the difference was statistically significant (P = 0.001). Despite no statistically significant differences in lipid profiles between the groups at the baseline, triglycerides were significantly higher in the OCs group compared to the phlebotomy at end of follow up (p = 0.019). CONCLUSION: Both treatment modalities had similar beneficial effects on insulin resistance and on androgenic profiles. However, OCs was reported more effective in treating menstrual irregularities and phlebotomy had less adverse effects on triglyceride concentrations. TRIAL REGISTRATION: Code: IRCT2013080514277N1 . PMID: 31470879 [PubMed - in process]
https://finance.yahoo.com/news/research-breakthrough-may-lead-early-190000532.html
Research Breakthrough May Lead To Early Diagnosis of PCOS
https://clinicaltrials.gov/ct2/show/NCT03059173?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=05%2F15%2F2019&lupd_d=14
Conditions : Polycystic Ovary Syndrome; Reproductive Medicine
Interventions : Dietary Supplement: Inofolic (r); Drug: Clomiphene Citrate; Dietary Supplement: placebo
Sponsors : University Hospital, Lille; Ministry of Health, France
Not yet recruiting
Interest of Myo-inositol Supplementation in Women With Polycystic Ovarian Syndrome
NCT03059173
Thu, 23 Feb 2017 12:00:00 EST
Last Update Posted: 05/29/19 07:39AM
https://academic.oup.com/jes/article/3/10/1858/5540438/
https://www.ncbi.nlm.nih.gov/pubmed/31583367?dopt=Abstract
Related Articles
Dysglycemia, Not Altered Sex Steroid Hormones, Affects Cognitive Function in Polycystic Ovary Syndrome.
J Endocr Soc. 2019 Oct 01;3(10):1858-1868
Authors: Jarrett BY, Vantman N, Mergler RJ, Brooks ED, Pierson RA, Chizen DR, Lujan ME
Abstract
Context: Polycystic ovary syndrome (PCOS) is a complex endocrine condition characterized by multiple reproductive and metabolic abnormalities. Because individual reproductive and metabolic abnormalities modulate working memory in the general population, there is growing interest in whether cognitive function is dually and negatively affected in PCOS.
Objective: To examine the association of reproductive and metabolic features with cognitive function in women with and without PCOS.
Design: An observational, cross-sectional study was conducted at an academic clinical research center in North America between 2006 and 2009. Common tests of working memory (i.e., manual dexterity, perceptual speed, and visuospatial ability) were performed by women with PCOS (n = 40) and control subjects (n = 40). Markers of sex steroid hormones, ovulatory function, and cardiometabolic health were also assessed.
Results: Reduced visuospatial ability was observed in women with PCOS compared with control subjects (P < 0.01). Reduced visuospatial ability was linked to higher levels of hemoglobin A1c in the entire study cohort, independent of body mass index or PCOS status. No associations were observed between visuospatial ability and reproductive features, after controlling for confounding variables. Conclusion: Our findings support a role for glycemic control, and not PCOS per se, in cognitive dysfunction in women of reproductive age. Additional studies are needed to understand the short- and long-term effects of dysglycemia on brain health in women with PCOS, given their increased propensity for metabolic comorbidities, compared with control subjects. PMID: 31583367 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT04029805?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=07%2F09%2F2019&lupd_d=14
Conditions : Polycystic Ovarian Syndrome; Insulin Resistance
Interventions : Combination Product: Combination of a plant extract (BSL_EP044) and Lactobacillus BSL_PS6; Combination Product: Placebo
Sponsor : Biosearch S.A.
Recruiting
Evaluation of a Combination of a Plant Extract and a Probiotic on Glucidic Metabolism in Women With PCOS and High Insulin Levels
NCT04029805
Tue, 23 Jul 2019 12:00:00 EDT
Last Update Posted: 07/23/19 07:01AM
https://www.spandidos-publications.com/10.3892/mmr.2019.10446
https://www.ncbi.nlm.nih.gov/pubmed/31322191?dopt=Abstract
miR‑28‑5p suppresses cell proliferation and weakens the progression of polycystic ovary syndrome by targeting prokineticin‑1.
Mol Med Rep. 2019 Jul 01;:
Authors: Meng L, Yang H, Jin C, Quan S
Abstract
Prokineticin‑1 (PROK1) serves important roles in the pathogenesis of polycystic ovary syndrome (PCOS); however, the association between microRNA (miR)‑28‑5p and PROK1 remains unclear. In the present study, the roles of miR‑28‑5p and PROK1, and their interaction in PCOS were investigated. Rat ovary granule cells were transfected with miR‑28‑5p mimics, and PROK1 expression levels were measured by reverse transcription‑quantitative PCR and western blotting. A dual‑luciferase reporter assay was performed to determine the association between miR‑28‑5p and PROK1. Additionally, pcDNA‑PROK1 was co‑transfected into rat ovary granule cells with miR‑28‑5p mimics. Cell proliferation, apoptosis, cell cycle and the expression of signaling proteins were investigated using Cell Counting Kit‑8 assays, 5‑ethynyl‑2’‑deoxyuridine staining, flow cytometry and western blotting, respectively. PROK1 expression was suppressed in rat ovary granule cells by miR‑28‑5p mimics, but upregulated following transfection with miR‑28‑5p inhibitors. The dual‑luciferase reporter assay revealed that miR‑28‑5p binds to the 3’‑untranslated region of PROK1. Proliferation activity was increased in PROK1‑overexpressing cells; this effect was eliminated by co‑transfection with miR‑28‑5p mimics. PROK1‑overexpressing rat ovary granule cells exhibited significantly suppressed cell apoptosis and a decreased number of cells in G1; miR‑28‑5p mimics reversed these effects. Western blotting revealed that the PI3K/AKT/mTOR signaling pathway was activated by PROK1. The present results suggested that miR‑28‑5p attenuated the progression of PCOS by targeting PROK1, which may promote the pathogenesis of PCOS via the PI3K/AKT/mTOR pathway, indicating that the miR‑28‑5p/PROK1 axis may be a potential therapeutic target for patients with PCOS.
PMID: 31322191 [PubMed – as supplied by publisher]
https://www.sciencedirect.com/science/article/pii/S102845591930107X?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/31307731?dopt=Abstract
Dyslipidemia involvement in the development of polycystic ovary syndrome.
Taiwan J Obstet Gynecol. 2019 Jul;58(4):447-453
Authors: Liu Q, Xie YJ, Qu LH, Zhang MX, Mo ZC
Abstract
Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.
PMID: 31307731 [PubMed – in process]
https://finance.yahoo.com/news/ablacare-announces-series-financing-10-145800238.html
AblaCare Announces Series A Financing of €10 Million by Sofinnova Partners for Innovative Infertility Treatment and Appoints Jodie Fam as CEO
Funds to Support European Feasibility Study for Device Designed to Restore Ovulation in Women with Infertility Related to Polycystic Ovary Syndrome
https://link.springer.com/article/10.1007%2Fs12253-019-00676-3
https://www.ncbi.nlm.nih.gov/pubmed/31278444?dopt=Abstract
Related Articles
A Novel Genes Signature Associated with the Progression of Polycystic Ovary Syndrome.
Pathol Oncol Res. 2019 Jul 05;:
Authors: He D, Liu L, Wang Y, Sheng M
Abstract
To identify genes involving in the pathogenesis of polycystic ovary syndrome (PCOS). In this study, the comprehensive analysis of GSE8157 was downloaded. Overlapping genes of differentially expressed genes (DEGs) were identified, and enrichment analysis for these genes was performed. A modular network of differentially expressed genes was constructed by weighted gene co-expression network analyses (WGCNA), and a total of 322 differentially expressed genes in 5 stable modules were screened. The correlations of genes of the stable modules in BioGRID 3.4, STRING 10.5, HPRD9 databases were screened, and the interaction network of 104 DEGs was constructed. In addition, some genes and the key words were searched in CTD. A total of 596 differentially expressed genes were screened, including 379 genes that were up-regulated in case group and down-regulated in control group and treat group, and 217 genes that were down-regulated in case group and up-regulated in control group and treat group. The differentially expressed genes were enriched in PPAR signaling pathway, Neuroactive ligand-receptor interaction, cAMP signaling pathway, of which pathways were involved in the cancer development. Finally, 7 important target genes were identified, such as APOC3 was interacted with pioglitazone, ADCY2 involved in cAMP signaling pathway, and the genes (C3AR1, HRH2, GRIA1, MLNR and TAAR2) involved in neuroactive ligand-receptor interaction. In addition, the important target genes were significantly differential expression. These results implied that the 7 important target genes were played an important role in the development and progression of PCOS. Our study implied that genes had played a key role in the development and progression of PCOS, the results showed that microarray can be use as a method for the discovery of new biomarkers and therapeutic targets for PCOS.
PMID: 31278444 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04009603?recrs=abdf&type=Intr&cond=Polycystic+Ovary+Syndrome&lupd_s=06%2F21%2F2019&lupd_d=14
Condition : Polycystic Ovary Syndrome
Interventions : Drug: Probiotic Agent; Drug: Metformin
Sponsor : Ziauddin University
Recruiting
Comparison of Probiotics, Metformin & Their Combination Therapy in the Treatment of PCOS
NCT04009603
Thu, 04 Jul 2019 12:00:00 EDT
Last Update Posted: 07/05/19 07:10AM
