Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

Title:Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

Volume: 22 Issue: 36

Author(s): David H. Abbott, Jon E. Levine and Daniel A. Dumesic

Affiliation:

Keywords: Androgen excess, developmental origins, fetal programming, Barker hypothesis, gestational hyperglycemia, lipotoxicity, animal models.

Abstract: Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.

Cite this article as:

Abbott H. David, Levine E. Jon and Dumesic A. Daniel, Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits, Current Pharmaceutical Design 2016; 22 (36) . https://dx.doi.org/10.2174/1381612822666160715133437