Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

Abstract

Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intrauterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.Reproduction (2015) 150 R11-R24

Effect of maternal PCOS and PCOS-like phenotype on the offspring's health

“…The premise of developmental origins of this syndrome is supported by the observation that girls born either small or large for gestational age may be at increased risk to manifest PCOS during reproductive life (Melo et al, 2010, Mumm et al, 2013). However, women born appropriate for gestational age can also develop PCOS, suggesting a multifactorial etiology (de Melo et al, 2015). A genetic susceptibility combined with an insult that occurs during intrauterine or early postnatal life may lead to reorganization of the neuroendocrine, ovarian, and metabolic systems that could culminate in disruptions observed in PCOS patients during adult life (Fig.…”

Prevalence, pathogenesis and management of prediabetes and type 2 diabetes mellitus in patients with polycystic ovary syndrome

“…changes in gene expression due to the presence of increased steroids, mostly androgens, during fetal development, also appears to increase the risk for IR, prediabetes and T2DM in offspring of patients with PCOS. 49 Emerging data suggest that the gut microbiome might also be implicated in the pathogenesis of impaired glucose metabolism in patients with PCOS.…”

Effects of Exogenous Adiponectin Supplementation in Early Pregnant PCOS Mice on the Metabolic Syndrome of Adult Female Offspring

“…Clinically, it is characterized by hyperandrogenemia, thin ovulation, and ovarian polycystic changes, often accompanied by insulin resistance and obesity [2,3]. The etiology of PCOS has not been clari ed yet, but, in recent years, more and more attention has been paid to the role of environmental and genetic factors in the occurrence and development of PCOS [4]. Family aggregation and twin studies have shown that PCOS has a strong heritable component [5].…”