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Polycystic ovary syndrome and its developmental origins

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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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Acknowledgments

Supported by USPHS grants P01 HD44232 and HD 41098 to VP, U01 HD 044650 to DAD, R01 RR013635 to DHA, P50 HD044405 and P51 RR 000167 to the National Primate Research Center, University of Wisconsin, Madison and Organon USA, Inc. This work was partially supported by the NICHD National Cooperative Program on Female Health and Egg Quality under cooperative agreement U01 HD044650.

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Authors and Affiliations

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

    Daniel A. Dumesic & David H. Abbott

  2. Department OB/GYN, University of Wisconsin, Madison, WI, 53792, USA

    Daniel A. Dumesic & David H. Abbott

  3. Reproductive Medicine and Infertility Associates, Woodbury, MN, 55125, USA

    Daniel A. Dumesic

  4. Department of Pediatrics, University of Michigan, Ann Arbor, MI, 48109, USA

    Vasantha Padmanabhan

  5. The Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, 48109, USA

    Vasantha Padmanabhan

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  1. Daniel A. Dumesic
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Correspondence to Daniel A. Dumesic.

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Dumesic, D.A., Abbott, D.H. & Padmanabhan, V. Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord 8, 127–141 (2007). https://doi.org/10.1007/s11154-007-9046-0

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