PCOS Forum

Research in Polycystic Ovary Syndrome Today and Tomorrow

Renato Pasquali; Elisabet Stener-Victorin; Bulent O. Yildiz; Antoni J. Duleba; Kathleen Hoeger; Helen Mason; Roy Homburg; Theresa Hickey; Steve Franks; Juha S. Tapanainen; Adam Balen; David H. Abbott; Evanthia Diamanti-Kandarakis; Richard S. Legro


Clin Endocrinol. 2011;74(4):424-433. 

In This Article

Impact of Metabolic Abnormalities on the Development of PCOS in a Non-human Primate Model

A foetal testosterone excess model for PCOS manifests metabolic defects in adult female as well as adult male rhesus monkeys.[49] Testosterone treatment of monkey dams results in mild-to-moderate maternal glucose intolerance that adds a metabolic perturbation to in utero testosterone exposure and may explain why both female- and male testosterone-exposed offspring exhibit metabolic defects in adulthood.[50,51] Testosterone-exposed female offspring also demonstrate subtle increases in foetal head growth and postnatal body weight, as well as indications of foetal hyperglycaemia and neonatal hyperinsulinaemia. Neonatal hyperinsulinaemia may synergize with infant hyperandrogenism in testosterone-exposed females to increase lipogenesis and muscle protein synthesis,[51] thus enhancing insulin-sensitive tissue mass that may contribute to increased adiposity and insulin resistance found in testosterone-exposed adults.[49] As insulin defects have been found in prepubertal daughters born to women with PCOS,[52] metabolic abnormalities during gestation may provide an important developmental contribution to the expression of PCOS phenotype.

The foetal programming hypothesis, however, while well defined in animal models, has yet to be confirmed in humans, despite two recent studies attempting to define foetal testosterone exposure in PCOS women. A long-term prospective study investigating a large cohort of unselected adolescents found that blood levels of testosterone from their mothers at 18 and 34–36 week gestation, and from an umbilical cord sample, were not related to the subsequent development of PCOS.[53] A separate study examining umbilical cord blood levels in newborns found unchanged testosterone, but diminished androstenedione and estradiol levels, in girls born to women with PCOS.[53] These negative data are not surprising because human foetuses are protected from maternal androgen excess of PCOS by placental aromatase, and umbilical cord blood testosterone and androstenedione levels do not reliably distinguish boys from girls,[53] despite male foetal androgen excess earlier in gestation. This animal model offers a unique method to explore the effects of the intrauterine milieu on the development of future metabolic and reproductive abnormalities and allows controlled manipulation and long-term follow-up of offspring in a manner that would be unethical and frankly impossible in humans.


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