A Unique Rodent Model of Cardiometabolic Risk Associated with the Metabolic Syndrome and Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-/anovulation and polycystic ovarian morphology, and is a complex endocrine disorder that also presents with features of the metabolic syndrome, including obesity, insulin resistance and dyslipidemia. These latter symptoms form cardiometabolic risk factors predisposing individuals to the development of type-2 diabetes and cardiovascular disease (CVD). To date, animal models to study PCOS in the context of the metabolic syndrome and CVD risk have been lacking. The aim of this study was to investigate the JCR:LA-cp rodent as an animal model of PCOS associated with the metabolic syndrome. Metabolic indices were measured at 6 and 12 wks, and reproductive parameters including ovarian morphology and estrous cyclicity were assessed at 12 wks or adulthood. At 6 wks of age, the cp/cp genotype of the JCR:LA-cp strain developed visceral obesity, IR, dyslipidemia (hypertriglyceridemia and hypercholesterolemia) compared to control animals. Serum testosterone (T) concentrations were not significantly different between groups at 6 wks of age. However at 12 wks, the cp/cp genotype had higher serum T concentrations, compared to control animals, and presented with oligo-ovulation, a decreased number of corpora lutea and an increased number of total follicles, in particular atretic and cystic follicles. The cardiometabolic risk factors in the cp/cp animals were exacerbated at 12 wks including obesity, insulin resistance and dyslipidemia. The results of this study demonstrate that the JCR:LA-cp rodent may be a useful PCOS-like model to study early mechanisms involved in the etiology of cardiometabolic risk factors in the context of both PCOS and the metabolic syndrome.