Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application.

TitleNaturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application.
Publication TypeJournal Article
Year of Publication2019
AuthorsAbbott, DH, Rogers, J, Dumesic, DA, Levine, JE
JournalMed Sci (Basel)
Volume7
Issue12
Date Published2019 Nov 27
ISSN2076-3271
Abstract

Indian rhesus macaque nonhuman primate models for polycystic ovary syndrome (PCOS) implicate both female hyperandrogenism and developmental molecular origins as core components of PCOS etiopathogenesis. Establishing and exploiting macaque models for translational impact into the clinic, however, has required multi-year, integrated basic-clinical science collaborations. Paradigm shifting insight has accrued from such concerted investment, leading to novel mechanistic understanding of PCOS, including hyperandrogenic fetal and peripubertal origins, epigenetic programming, altered neural function, defective oocytes and embryos, adipogenic constraint enhancing progression to insulin resistance, pancreatic decompensation and type 2 diabetes, together with placental compromise, all contributing to transgenerational transmission of traits likely to manifest in adult PCOS phenotypes. Our recent demonstration of PCOS-related traits in naturally hyperandrogenic (High T) female macaques additionally creates opportunities to employ whole genome sequencing to enable exploration of gene variants within human PCOS candidate genes contributing to PCOS-related traits in macaque models. This review will therefore consider Indian macaque model contributions to various aspects of PCOS-related pathophysiology, as well as the benefits of using macaque models with compellingly close homologies to the human genome, phenotype, development and aging.

DOI10.3390/medsci7120107
Alternate JournalMed Sci (Basel)
PubMed ID31783681
Grant ListP50 HD028934 / NH / NIH HHS / United States
P50 HD044405 / NH / NIH HHS / United States
P50 HD071836 / NH / NIH HHS / United States
P51 OD011106 / NH / NIH HHS / United States
P50 HD071836 / HD / NICHD NIH HHS / United States