Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Early origins of polycystic ovary syndrome

Daniel A. Dumesic* A C D , R. Dee Schramm* A and David H. Abbott* A B

A Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.

B Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA.

C Departments of Obstetrics and Gynecology and Internal Medicine, The Mayo Clinic, Rochester, MN 55905, USA.

D Corresponding author. Email: danieldumesic@aol.com

Reproduction, Fertility and Development 17(3) 349-360 https://doi.org/10.1071/RD04092
Submitted: 26 April 2004  Accepted: 29 November 2004   Published: 14 February 2005

Abstract

The prenatally androgenised female rhesus monkey has become a model for polycystic ovary syndrome (PCOS) in women, with early prenatal androgenisation entraining a permanent PCOS-like phenotype characterised by luteinising hormone (LH) hypersecretion due to reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess associated with increased abdominal adiposity. These combined reproductive and metabolic abnormalities occur in combination with ovarian hyperandrogenism and follicular arrest in adulthood, and with premature follicle differentiation and impaired embryo development during gonadotrophin therapy for in vitro fertilization (IVF). The ability of prenatal androgen excess in fetal rhesus monkeys to entrain multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programmes target tissue differentiation, raising the possibility that hyperandrogenism in human fetal development promotes PCOS in adulthood. This hypothesis developed in prenatally androgenised female rhesus monkeys, however, also must include data from clinical studies of PCOS to clarify the homology between human and non-human primates in intrafollicular steroidogenesis and its impact on oocyte developmental competency. By doing so, future studies promise to develop new clinical strategies that will lead to improved pregnancy outcome and reduced pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus.

Extra keywords: adiposity, hyperandrogenism, hyperinsulinaemia, insulin receptor, luteinising hormone, prenatal androgenisation.


Acknowledgments

The authors wish to thank Rebekah R. Herrmann for preparation of the manuscript and Bob Becker for his contribution towards preparation of the figures. All human studies were approved by the Mayo Institutional Review Board. Non-human primates at the WPRC were maintained in accordance with the recommendations of the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and experimental protocols were reviewed and approved by the Graduate School Animal Care and Use Committee of the University of Wisconsin–Madison. The WPRC is accredited by AAALAC as part of the UW-Madison Graduate School. This work was supported by the National Institutes of Health Grants U01 HD044650–01 and R01 RR 13635, Mayo Clinical Research Grant 2123–01, Mayo Grant M01-RR-00585, Grant P51 RR 000167 to the National Primate Research Center, University of Wisconsin, Madison and Serono Pharmaceuticals.


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* Drs Dumesic, Schramm and Abbott contributed equally to this manuscript.


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