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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]