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Reviews in Endocrine and Metabolic Disorders
Published in: Reviews in Endocrine and Metabolic Disorders 2/2007

01-06-2007

Polycystic ovary syndrome and its developmental origins

Authors: Daniel A. Dumesic, David H. Abbott, Vasantha Padmanabhan

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 2/2007

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Abstract

The prenatal testosterone (T)-treated adult female rhesus monkey is one animal model of polycystic ovary syndrome (PCOS) in women, with early prenatal T excess programming a permanent PCOS-like phenotype characterized by luteinizing hormone (LH) hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess from increased abdominal adiposity. These combined reproductive and metabolic abnormalities are associated with ovarian hyperandrogenism and follicular arrest in adulthood, as well as premature follicle differentiation and impaired embryo development during gonadotropin therapy for in vitro fertilization (IVF). A second animal model for PCOS, the prenatal T-treated sheep also is characterized by LH hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback, persistent follicles and insulin resistance, but also is associated with intrauterine growth retardation and compensatory growth after birth. The ability of prenatal T excess in both species to alter the developmental trajectory of multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programs target tissue differentiation, raising the possibility that T excess in human fetal development promotes PCOS in adulthood. Such a hypothesis must include data from clinical studies of PCOS women to clarify the homology between these PCOS-like animal models and PCOS per se in reproductive and metabolic function. Future studies should develop new clinical strategies that improve pregnancy outcome and minimize pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus as well as minimize transgenerational susceptibility to adult PCOS and its metabolic derangements in male close relatives.
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Metadata
Title
Polycystic ovary syndrome and its developmental origins
Authors
Daniel A. Dumesic
David H. Abbott
Vasantha Padmanabhan
Publication date
01-06-2007
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 2/2007
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-007-9046-0

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