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Polycystic Ovary Syndrome: Guinea Pigs as a Potential Model of Mild Hyperandrogenemia

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  • Polycystic Ovary Syndrome (PCOS) is an idiopathic disorder prevalent in ~5-10% of reproductive-aged women. In PCOS women who become pregnant, many experience complications including increased susceptibility of having a miscarriage, high blood pressure, and gestational diabetes, among others. Additionally, exposure to PCOS may have transgenerational impacts: offspring may be at increased risk of overall poor health in adulthood. Many models of PCOS have been developed, such as the sheep and rodent animal models; yet these models do not provide a good foundation to study PCOS as it would appear in women, and to understand the effects inflicted on offspring later in life. In previous studies, a nonhuman primate model of PCOS which exposed rhesus monkeys to mildly elevated testosterone (T) with and without a high fat diet (HFD) during early adolescence developed many PCOS-like symptoms; however, transgenerational studies in macaques were challenging to pursue due to longer generational intervals (5+ years). We hypothesize the guinea pig sow is a good surrogate for primates and will show a similar PCOS like phenotype. Eight Hartley Guinea Pigs were obtained prior to puberty, and had subcutaneous implants placed containing either cholesterol (n=4) or T (n=4) at 1 month of age and again at 3 months of age. Serum T levels and weight were assessed weekly, and females were monitored for signs of estrus periodically. At 5 months of age, after 16 weeks of treatment, all females were necropsied, and tissues of interest were analyzed, and some collected for histology. The T-treated females did not differ in body weight by age or compared to the controls, similar to previous studies in rhesus monkeys. After the end of the eight weeks, the levels of serum T remained 2.01 +/- 0.5-fold increase above female guinea pigs in the cholesterol control group. Further analyses are ongoing, but these results suggest the guinea pig sow may be a good surrogate model of mild hyperandrogenemia, similar to women with PCOS.
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