Hyperandrogenism and phenotypes of polycystic ovary syndrome are not associated with differences in obstetric outcomes

Mumm, Hanne; Jensen, Dorte Møller; Sørensen, Jens Aage; Andersen, Lise Lotte Torvin; Ravn, Pernille; Andersen, Marianne; Glintborg, Dorte

doi:10.1111/aogs.12545

Cited by 40 publications

(50 citation statements)

References 35 publications

(43 reference statements)

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“…The effect of locus determined by GWAS lasts a lifetime, but the epigenetic changes are dynamic during growth process. [21,22] Studies have suggested that DNA methylation regulation exists in ovarian follicle growth and atresia. [23] YAP1, known as a pivotal transcriptional co-activator of Hippo pathway, participates in many signaling pathways that regulate organic morphology, including ovary enlargement that is one of the major manifestations of PCOS.…”

Section: Discussionmentioning

confidence: 99%

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

et al. 2017

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Background:DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS.Methods:Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR.Results:Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (−443, −431, −403, −371, −331, −120, −49, −5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose–dependent relation.Conclusion:Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

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Section: Discussionmentioning

confidence: 99%

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

et al. 2017

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“…Eighteen studies were conducted in Europe, 36,37,42,43,50,51,53,54,57,60,64,75,76,[79][80][81][82]91 16 in Americas, 23,31,32,34,38,39,45,47,49,52,56,58,61,65,72,87 23 in Asia, 30,33,35,44,46,48,55,59,62,66,67,69,70,73,74,77,[83][84]…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity—A systematic review, meta‐analysis, and meta‐regression

et al. 2019

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Summary Polycystic ovary syndrome (PCOS) is associated with an increased risk of maternal pregnancy and delivery complications. However, the impact of clinical features of PCOS and other potential risk factors in PCOS is still unknown. We aimed to investigate the association of PCOS with maternal pregnancy and delivery complications with consideration of risk factors and potential confounders. The meta‐analysis included 63 studies. PCOS was associated with higher miscarriage, gestational diabetes mellitus, gestational hypertension, pre‐eclampsia, induction of labour, and caesarean section. The association of PCOS with these outcomes varied by geographic continent, PCOS phenotypes, and study quality. Pre‐eclampsia and induction of labour were not associated with PCOS on body mass index‐matched studies. No outcome was associated with PCOS on assisted pregnancies. Age was significantly associated with higher miscarriage on meta‐regression. There were no studies assessing perinatal depression. We confirm that PCOS is associated with an increased risk of maternal pregnancy and delivery complications. The association of PCOS with the outcomes is worsened in hyperandrogenic PCOS phenotypes, in specific geographic continents, and in the highest quality studies but disappears in assisted pregnancies. Future studies in PCOS are warranted to investigate proper timing for screening and prevention of maternal pregnancy and delivery complications with consideration of clinical features of PCOS.

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“…There is limited research exploring this hypothesis. Some studies indicate that a combination of hyperandrogenism and IR and/or hyperinsulinemia may result in increased risk of adverse pregnancy outcomes in women with PCOS such as pregnancy loss, foetal growth abnormalities, GDM, GH, PE, preterm birth and antepartum haemorrhage through altering normal placental implantation . Adverse maternal and neonatal complications were assessed in a study of 885 primiparous women and controls (n = 85 PCOS by NIH, n = 78 PCOS only by Rotterdam, n = 14 PCOS only by the Androgen Excess and PCOS Society criteria and n = 708 controls) .…”

Section: Possible Contributing Mechanisms Of Pcos In Adverse Pregnancmentioning

confidence: 99%

“…Animal studies suggest that hyperandrogenism may disturb foetal growth 33 ; however, it may alternatively increase foetal size if presenting with IR/hyperinsulinemia. 34 On the other hand, chronic hyperinsulinemia may restrict foetal growth through interfering with normal vascular function. 35 Different cut-off points used for defining hyperandrogenism and hyperinsulinemia across studies could therefore contribute to diverse results.…”

Section: Foetal and Infant Complicationsmentioning

confidence: 99%

Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of knowledge, challenges and potential implications for practice

Khomami

Boyle

Tay

et al. 2018

Clinical Endocrinology

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Summary Although there is a growing body of literature reporting that pregnancies in women with polycystic ovary syndrome (PCOS) are associated with greater complications than those without PCOS, methodological differences across studies make these results difficult to consolidate. This narrative review outlines potential mechanisms involved in adverse pregnancy outcomes in PCOS and the nature of the complications. It covers limitations of current evidence and future research directions. Future research should include prospective studies with phenotypic stratification of PCOS and matching or consideration of specific PCOS manifestations and risk factors specific to each pregnancy complication. This review also emphasizes the importance of following a healthy lifestyle for women with PCOS and of individualized care according to overall risk factors for pregnancy complications.

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Hyperandrogenism and phenotypes of polycystic ovary syndrome are not associated with differences in obstetric outcomes

Abstract: Obstetric outcomes were comparable in women with different PCOS phenotypes.

Cited by 40 publications

References 35 publications

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity—A systematic review, meta‐analysis, and meta‐regression

Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of knowledge, challenges and potential implications for practice

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