Differential Strain-dependent Ovarian and Metabolic Responses in a Mouse Model of PCOS.

Several mouse models have been developed to study polycystic ovarian syndrome (PCOS), a leading cause of infertility in women. Treatment of mice with DHT for 90 days causes ovarian and metabolic phenotypes similar to women with PCOS. We used this 90-day DHT treatment paradigm to investigate the variable incidence and heterogeneity in 2 inbred mouse strains, NOD/ShiLtJ and 129S1/SvlmJ. NOD mice naturally develop type 1 diabetes, and recent meta-analysis found increased androgen excess and PCOS in women with type 1 diabetes. The 129S1 mice are commonly used in genetic manipulations. Both NOD and 129S1 DHT-treated mice had early vaginal opening, increased anogenital distance, and altered estrus cycles compared with control animals. Additionally, both NOD and 129S1 mice had reduced numbers of corpora lutea after DHT exposure, whereas NOD mice had decreased numbers of preantral follicles and 129S1 mice had reduced numbers of small antral follicles. NOD mice had increased body weight, decreased white adipocyte size, and improved glucose sensitivity in response to DHT, whereas 129S1 mice had increased body weight and white adipocyte size. NOD mice had increased expression of Adiponectin, Cidea, Srebp1a, and Srebp1b and 129S1 mice had decreased Pparg in the white adipose tissues, whereas both NOD and 129S1 mice had increased expression of Glut4 and Prdm16, suggesting DHT may differentially affect glucose transport, thermogenesis, and lipid storage in white adipose tissue. DHT causes different ovarian and metabolic responses in NOD and 129S1 mice, suggesting that strain differences may allow further elucidation of genetic contributions to PCOS.

Rodent models of mental illness in polycystic ovary syndrome: the potential role of hypothalamic-pituitary-adrenal dysregulation and lessons for behavioral researchers.

Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, with phenotypes including ovarian and metabolic dysfunctions. Women with PCOS also show increased rates of mental illness, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and altered responsiveness to stressors that may contribute to the higher rates of mental illness, specifically depression and anxiety. Animal models of PCOS have provided insight into the ovarian and metabolic mechanisms that underlie the syndrome, and several models have been used to study the behavioral consequences associated with PCOS in the laboratory. Several studies in rodent models of PCOS demonstrate changes in anxiety-like behavior, but researchers often neglect to report procedural details or behavioral data crucial to interpreting the differences observed in those studies. Additionally, the impact of potential HPA dysregulation in animal models of PCOS may influence behavioral findings, although only three studies to date have examined this. As such, researchers should consider and report stress-associated variables (e.g., time of day, light/dark cycle, light intensity, housing, and procedures to control experimenter and litter effects) that may influence depression- and anxiety-like behaviors in rodents. This review will summarize the behavioral and HPA-related studies in women with PCOS and rodent models of the disease, and provide considerations for future studies.