Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 22, Issue 36, Pages 5625-5633Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612822666160715133437
Keywords
Androgen excess; developmental origins; fetal programming; Barker hypothesis; gestational hyperglycemia; lipotoxicity; animal models
Categories
Funding
- NIH [P50 HD044405, P50 HD028934, P50 HD071836, P51 OD011106]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P50HD071836, P50HD044405, P50HD028934] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P51OD011092, P51OD011106] Funding Source: NIH RePORTER
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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 new-born females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.
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