Developmental origins and transgenerational inheritance of polycystic ovary syndrome

Abstract

There has been increasing awareness that polycystic ovary syndrome (PCOS) phenotypes may represent a mismatch between ancient genetically programmed metabolic and reproductive survival mechanisms and modern lifestyle practices. In-utero developmental programming of metabolic and endocrine pathways may play an important role in activating gene variants that predispose the offspring to develop PCOS when exposed to specific postnatal conditions. Postnatal exposure to lifestyle factors such as poor-quality diet and endocrine disrupting chemicals may modulate epigenetically programmed pathways that result in the observed pathophysiological changes and clinical features seen in women with PCOS. To review the developmental origins and transgenerational transmission of PCOS and the impact of lifestyle, androgens and endocrine disrupting chemicals on fetal epigenetic programming. The literature was reviewed using Google, Google Scholar, Medline and PubMed databases. The results are presented as a narrative review. Human observational and animal experimental data support the hypothesis that PCOS is an inherited condition that arises as a result of developmental programming of normal gene variants. It is likely that these genes can be amplified by in-utero androgen exposure and activated by a range of postnatal lifestyle and environmental factors. Endocrine disrupting chemicals have the potential to influence developmental programming of PCOS susceptibility genes. The current evidence suggests that developmental epigenetic programming following exposure to an adverse maternal metabolic and endocrine environment contributes to the pathogenesis of PCOS. Lifestyle interventions, as recommended by the International Guidelines, have the potential to reduce both symptoms and transgenerational transmission of PCOS.