Current concepts of polycystic ovary syndrome pathogenesis

Current Opinion in Pediatrics, Год журнала: 2020, Номер 32(5), С. 698 - 706

Опубликована: Сен. 3, 2020

Purpose of review This provides a model for understanding polycystic ovary syndrome (PCOS) pathophysiology and updates the evidence on which it is based. Then, highlights complimentary molecular genetic epigenetic advances in PCOS cause. Recent findings Important studies into cause built 2014 discovery novel regulatory protein variant that underlies typical steroidogenic abnormalities: DENND1A.V2 (differentially expressed normal neoplastic development, isoform 1A, 2). Over 30 DENND1A gene variants have been found, vast majority upstream coding sequence potentially regulatory. These are individually uncommon but collectively plausibly 50% PCOS. Anti-Müllerian hormone (AMH)/AMH receptor with decreased function possibly 6.7% DENNND1A was recently reported to belong signaling network upregulates luteinizing expression insulin mitogenic signaling. Prenatal androgen administration has proven be potent regulator causes transgenerational epigenomic changes mouse similarities those human daughters. Summary In addition finding how contribute pathogenesis, better mechanisms action diverse tissues can expected expand our pathogenesis.

Язык: Английский

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PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Апрель 30, 2020

Polycystic ovary syndrome is characterized by reproductive and metabolic disturbances throughout the female lifespan. Therefore, this study aimed to determine whether genome-wide association studies (GWAS)-identified risk variants for PCOS could confer of (MS) or insulin resistance (IR). Fifteen independent SNPs mapping 11 GWAS loci genotyped in a total 2082 Han Chinese women previous phenotype-genotype correlations were assessed. The CC group rs12478601 THADA was associated with decreased rate MS after adjustment age (23.2% vs 27%, P = 0.042, OR 0.81). Using dominant model, GG+AG rs2059807 INSR increased (26.8% 22.5%, 0.023, 1.27). GG + GT rs4784165 TOX3 found be an IR BMI(53.3% 48.5%, 0.027, 1.27).The rs2479106 DENND1A (48.3% 53.6%, adjusted 0.039, 0.80). After exclusion cases family history diabetes, hypertension, dyslipidemia, between genes still significant (P < 0.05). Three (rs13429458 THADA, rs10818854 DENND1A, INSR) significantly IR; however, their not BMI. This genotype-phenotype thus provides clues that INSR, TOX3, play role possibly through disorder-related pathway.

Язык: Английский

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Combined oral contraceptive pill compared with no medical treatment in the management of polycystic ovary syndrome: A systematic review

Clinical Endocrinology, Год журнала: 2023, Номер 99(1), С. 79 - 91

Опубликована: Март 20, 2023

Abstract Objective As part of the update International Evidence‐Based Guidelines for Assessment and Management polycystic ovary syndrome (PCOS), a systematic review was performed to inform evidence‐based recommendations. Design Systematic review. Only randomised controlled trial were included. Patients Women with PCOS; use combined oral contraceptive pills (COCP) compared no medical treatment. Measurements Outcomes designed in collaboration clinical experts, researchers, consumers. Critical outcomes included hirsutism, irregular cycles, quality life, body mass index (BMI), weight. Results 1660 publications identified, but only four studies No could be meta‐analysis. COCP treatment improved cycle regularity (100% vs. 0%, low certainty evidence). showed difference improvement hirsutism or BMI placebo lifestyle; lower weight after (mean [MD] −8.0 (95% confidence interval, CI −11.67); −4.33 kg); life (MD 1.2 [95% 0.96]; 1.44), these results all very evidence. Conclusion show that benefit regulation, other benefits potential adverse effects identified The is frontline PCOS, this still based on established efficacy broader general population. Our research PCOS seriously lacking should prioritised capture core reproductive, metabolic psychological important PCOS.

Язык: Английский

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Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Фев. 26, 2024

Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous notable differences between lean and obese women, implying different pathophysiology manifesting in differential body mass index (BMI). We performed meta-analysis genome-wide association study (GWAS) data from six well-characterised cohorts, using case-control design stratified by BMI, aiming to identify variants associated overweight/obese subtypes.

Язык: Английский

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Whole exome sequencing uncovers rare variants associated with PCOS susceptibility in Indian women

Systems Biology in Reproductive Medicine, Год журнала: 2025, Номер 71(1), С. 76 - 89

Опубликована: Март 14, 2025

Polycystic ovary syndrome (PCOS) is a complex polygenic endocrinopathy affecting 5–20% of reproductive-age women. Familial studies, candidate gene and GWAS have identified multiple PCOS-associated genetic loci. This study aims to identify the functional variants associated with PCOS. We applied whole exome sequencing (WES) among eighty-five well-characterized women The annotated were filtered based on minor allele frequency in-silico pathogenicity prediction. found significant association 234 rare pathogenic nonsynonymous in 201 genes PCOS our group. These are linked steroid hormone biosynthesis, ovarian steroidogenesis, insulin resistance, PI3K-Akt signaling pathway which influential pathophysiology. Further, several be unique without enrichment analysis revealed that carbohydrate lipid metabolism was especially deranged insulin-resistant Variants steroidogenesis validated by Sanger including rs368902124 (CYP19A1), rs143286842 (IGF1R), rs555458296 (BMP-6). In-silico DUET showed these destabilized folding their corresponding protein. Women carrying presented altered hormonal profiles clinical signs hyperandrogenism hyperinsulinemia, emphasizing impact Several been increased risk present thus, expanding susceptibility landscape Indian

Язык: Английский

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Suppression of PCSK9/NF-kB-dependent pathways by acetate ameliorates cardiac inflammation in a rat model of polycystic ovarian syndrome

Life Sciences, Год журнала: 2022, Номер 300, С. 120560 - 120560

Опубликована: Апрель 19, 2022

Язык: Английский

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Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

Medical Sciences, Год журнала: 2019, Номер 7(12), С. 107 - 107

Опубликована: Ноя. 27, 2019

Indian rhesus macaque nonhuman primate models for polycystic ovary syndrome (PCOS) implicate both female hyperandrogenism and developmental molecular origins as core components of PCOS etiopathogenesis. Establishing exploiting translational impact into the clinic, however, has required multi-year, integrated basic-clinical science collaborations. Paradigm shifting insight accrued from such concerted investment, leading to novel mechanistic understanding PCOS, including hyperandrogenic fetal peripubertal origins, epigenetic programming, altered neural function, defective oocytes embryos, adipogenic constraint enhancing progression insulin resistance, pancreatic decompensation type 2 diabetes, together with placental compromise, all contributing transgenerational transmission traits likely manifest in adult phenotypes. Our recent demonstration PCOS-related naturally (High T) macaques additionally creates opportunities employ whole genome sequencing enable exploration gene variants within human candidate genes models. This review will therefore consider model contributions various aspects pathophysiology, well benefits using compellingly close homologies genome, phenotype, development aging.

Язык: Английский

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Sequencing-based genome-wide association studies reporting standards

Cell Genomics, Год журнала: 2021, Номер 1(1), С. 100005 - 100005

Опубликована: Окт. 1, 2021

Genome sequencing has recently become a viable genotyping technology for use in genome-wide association studies (GWASs), offering the potential to analyze broader range of variation, including rare variants. To survey current standards, we assessed content and quality reporting statistical methods, analyses, results, datasets 167 exome- or genome-wide-sequencing-based GWAS publications published from 2014 2020; 81% included tests aggregate across multiple variants, with test models frequently used. We observed lack standardized terms incomplete datasets, particularly variants analyzed tests. also find lower frequency sharing summary statistics compared array-based GWASs. Reporting standards increased data are required ensure sequencing-based study findable, interoperable, accessible, reusable (FAIR). support that, recommend adopting standard terminology (seqGWAS). Further, that single-variant analyses be reported following same conventions as GWASs shared Catalog. provide initial recommended metadata statistics.

Язык: Английский

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The contribution of rare genetic variants to the pathogenesis of polycystic ovary syndrome

Current Opinion in Endocrine and Metabolic Research, Год журнала: 2020, Номер 12, С. 26 - 32

Опубликована: Апрель 4, 2020

Язык: Английский

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Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto’s Thyroiditis: How Far Is Our Understanding?

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Фев. 26, 2021

Polycystic ovary syndrome (PCOS) and Hashimoto’s thyroiditis (HT) are endocrine disorders that commonly occur among young women. A higher prevalence of HT in women with PCOS, relative to healthy individuals, is observed consistently. Combined occurrence both diseases associated a risk severe metabolic reproductive complications. Genetic factors strongly impact the pathogenesis PCOS several susceptibility loci have been identified. Furthermore, some candidate gene polymorphisms thought be functionally relevant; however, few genetic variants proposed causally incidence together.

Язык: Английский

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