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Abstract: Polycystic ovary syndrome (PCOS) is a fertility disorder affecting 5–7% of reproductive-aged women. Women with PCOS manifest both reproductive and metabolic defects. Several animal models have evolved, which implicate excess steroid exposure during fetal life in the development of the PCOS phenotype. This review addresses the fetal and adult reproductive and metabolic consequences of prenatal steroid excess in sheep and the translational relevance of these findings to PCOS. By comparing findings in various breeds of sheep, the review targets the role of genetic susceptibility to fetal insults. Disruptions induced by prenatal testosterone excess are evident at both the reproductive and metabolic level with each influencing the other thus creating a self-perpetuating vicious cycle. The review highlights the need for identifying a common mediator of the dysfunctions at the reproductive and metabolic levels and developing prevention and treatment interventions targeting all sites of disruption in unison for achieving optimal success. [Copyright &y& Elsevier]

Abstract: Findings discussed in this review stress the importance of normal estrogen and androgen signaling at appropriate developmental time points in maintaining normal phenotypic expression, reproductive and metabolic function and document how inappropriate steroid signaling, at inopportune times can have undesirable outcomes. For example, inappropriate testosterone exposure during fetal life alters the developmental trajectory of the female culminating in a suite of disorders, which include intrauterine growth-retardation and postnatal catch up growth, phenotypic masculinization, reproductive neuroendocrine and ovarian disruptions leading to progressive loss of cyclicity and metabolic disruptions manifested as hyperinsulinemia. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: The timing of puberty generally differs between sexes, and this may be due to sex differences in the organization of steroid feedback systems. We propose that the reproductive neuroendocrine default sex is female. If the individual is male, the feedback control of GnRH secretion is programmed early in development, and the pubertal GnRH rise is either advanced or delayed depending upon species. This developmental programming is by androgens. Early programming also reorganizes adult reproductive neuroendocrine function to change a pattern of cyclic gamete release (periodic ovulations) requiring multiple feedback systems to that of a continuous one (spermatogenesis) requiring only the negative feedback control. The multiple feedback systems underlying the complex ovulatory cycle are innate, and in the male the unnecessary feedbacks are abolished or rendered less sensitive during development by the estrogenic, as well as the androgenic metabolites of testosterone. [Copyright &y& Elsevier]