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

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities affecting women of reproductive age. While the exact origin of PCOS is unknown, observations from clinical and animal studies suggest that maternal hyperandrogenism may be a contributing factor. Because women with PCOS manifest hyperandrogenism during pregnancy, changes in the gestational endocrine milieu may play a role in the vertical transmission of this syndrome. This review discusses the potential developmental origins of PCOS, the impact of maternal PCOS on the offspring's health and contributions of the postnatal environment, capitalizing on findings from animal models that exhibit a PCOS-like phenotype. In addition, this review highlights the scarcity of data at early gestational stages in humans and the importance of animal experimentation to better understand the cellular and molecular mechanisms involved in the programming of adult diseases, therefore, helping identify therapeutic targets for preventive and treatment strategies.

Keywords: Androgen; Animal models; Developmental programming; Insulin; Polycystic ovary syndrome.

Figure 1

Schematic showing the timeline of the organizational and activational effects that program adult onset disorders. In addition to genetic susceptibility, environmental changes and/or lifestyle choices have the potential to elicit changes in the maternal milieu and lead to epigenetic alterations that contribute to organizational changes during early development. Once organizational events are completed, programmed alterations in endocrine system, environmental and lifestyle factors can then influence the manifestation and severity of adult onset diseases through activational changes that may or may not involve epigenetic alterations.

Figure 2

Schematic of the “two-hit hypothesis” for development and manifestation of PCOS-like traits in females. Known changes in prenatal, early postnatal, and adult life in offspring of PCOS women, as well as in the monkey and sheep models for PCOS are shown. Prenatal insults (“first-hit”) in conjunction with postnatal insults (“second-hit”) may be involved in the pathogenesis of PCOS. Observations in prenatal testosterone treated sheep and rhesus monkeys support the premise that postnatal endocrine and metabolic alterations play a role in maintaining/amplifying the PCOS-like traits in these females.