The role of TGF-? in polycystic ovary syndrome.
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ABSTRACT:
SUBMITTER: Raja-Khan N
PROVIDER: S-EPMC5933191 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
The role of TGF-β in polycystic ovary syndrome.
Raja-Khan Nazia N Urbanek Margrit M Rodgers Raymond J RJ Legro Richard S RS
Reproductive sciences (Thousand Oaks, Calif.) 20130412 1
Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligoanovulation and hyperandrogenism and associated with insulin resistance, type 2 diabetes, and cardiovascular risk. In recent years, genetic studies have linked PCOS to a dinucleotide marker D19S884 in the fibrillin 3 gene. Fibrillins make up the major component of microfibrils in the extracellular matrix (ECM) and interact with molecules in the ECM to regulate transforming growth factor β (TGF-β) signal ...[more]
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Project description:Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-? activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-? bioactivity in tissues by binding latent TGF-? binding proteins. We therefore examined expression of fibrillins 1-3, latent TGF-? binding proteins 1-4, and TGF-? 1-3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-? pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.
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Project description:BackgroundPolycystic ovary syndrome (PCOS) is a widespread endocrine disorder, affecting approximately 20% of women within reproductive age. It is associated with hyperandrogenism, obesity, menstrual irregularity, and anovulatory infertility. Melatonin is the main pineal gland hormone involved in the regulation of the circadian rhythm. In recent years, it has been observed that a reduction in melatonin levels of follicular fluid exists in PCOS patients. Melatonin receptors in the ovary and intra-follicular fluid adjust sex steroid secretion at different phases of ovarian follicular maturation. Moreover, melatonin is a strong antioxidant and an effective free radical scavenger, which protects ovarian follicles during follicular maturation.ObjectiveIn this paper, we conducted a literature review and the summary of the current research on the role of melatonin in PCOS.Materials and methodsElectronic databases including PubMed/MEDLINE, Web of Science, Scopus, and Reaxys were searched from their inception to October 2018 using the keywords "Melatonin" AND "Polycystic ovary syndrome" OR "PCOS."ResultsBased on the data included in our review, it was found that the administration of melatonin can improve the oocyte and embryo quality in PCOS patients. It may also have beneficial effects in correcting the hormonal alterations in PCOS patients.ConclusionSince metabolic dysfunction is the major finding contributing to the initiation of PCOS, melatonin can hinder this process via its improving effects on metabolic functions.
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Project description:Polycystic ovary syndrome (PCOS) is a highly complex endocrine disorder, characterized by hyperandrogenemia, menstrual irregularities and polycystic ovaries. A strong genetic component to the etiology of PCOS is evident. However, due to the genetic and phenotypic heterogeneity of PCOS and the lack of insufficiently large cohorts, studies to identify specific contributing genes to date have yielded only few conclusive results. In this review we discuss the current status of the genetic analysis of PCOS including the results of numerous association studies with candidate genes involved in TGF-β and insulin signaling, type 2 diabetes mellitus and obesity susceptibility. Furthermore, we address current challenges in genetic studies of PCOS, and the promise of new approaches, including genome-wide association studies and next-generation sequencing.
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