Reviews in Endocrine and Metabolic Disorders

, Volume 8, Issue 2, pp 127–141

Polycystic ovary syndrome and its developmental origins

  • Daniel A. Dumesic
  • David H. Abbott
  • Vasantha Padmanabhan
Article

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.

Keywords

Prenatal androgenization Polycystic ovary syndrome Luteinizing hormone Hyperandrogenism Hyperinsulinemia Adiposity 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Daniel A. Dumesic
    • 1
    • 2
    • 3
  • David H. Abbott
    • 1
    • 2
  • Vasantha Padmanabhan
    • 4
    • 5
  1. 1.Wisconsin National Primate Research CenterUniversity of WisconsinMadisonUSA
  2. 2.Department OB/GYNUniversity of WisconsinMadisonUSA
  3. 3.Reproductive Medicine and Infertility AssociatesWoodburyUSA
  4. 4.Department of PediatricsUniversity of MichiganAnn ArborUSA
  5. 5.The Reproductive Sciences ProgramUniversity of MichiganAnn ArborUSA

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