CONICET | Buscador de Institutos y Recursos Humanos

Polycystic Ovary Syndrome (PCOS) is an endocrine disease characterized by hyperandrogenism, oligo-anaovulation and/or polycystic ovaries. It is associated to infertility, obesity, metabolic disorders and chronic low-grade inflammation. The study of PCOS has been largely constrained by the lack of an animal model that reflects its heterogeneity. Therefore, the aim of this work was to establish if dehydroepiandrosterone (DHEA)-androgenization model is suitable to study the immune alterations related to PCOS. 30-day-old female BALB/c mice were daily injected for 20 days with DHEA or vehicle (Control group). Analysis of ovarian histological sections stained for H&E showed that the 71% (5/7) of DHEA treated animals developed 1-3 cystic follicles, considered as enlarge follicles with an attenuated and compacted granulose-cell layer. Serum estradiol (E) levels, determined by ELISA, were found increased after DHEA treatment (Control: 11±1 vs DHEA: 22±6 pg/ml, p< 0,05, n=7) as well as body weights (19,6±0,6 vs 21,5±0,9 g, p< 0,05). During the experiment control animals began to have irregular cycles while androgenized mice exhibited permanently estrous or metaestrous stages. Flow cytometry analysis of blood showed an increased frequency of CD4+CD25+ activated/regulatory T cells and CD4+CD49b+ NKT CD4+ cells while total CD4+ cells remained unaltered after DHEA treatment. DHEA treated mice display key features of PCOS, such as ovarian cysts, estrous cycle arrest and increased E levels and body weight. Also the immune cell populations studied show the same tendency found in PCOS women, indicating that DHEA androgenization in mice may constitute an appropriate model to study immune imbalance in PCOS.