Insights from a novel mouse model for Polycystic Ovary Syndrome (PCOS):systemic inflammation and up-regulation of adhesion moleculeexpression in ovaries is associated with clinical symptoms

MARIA EMILIA SOLANO; EVELIN HAGEN; ALICIA BEATRIZ MOTTA; PETRA ARCK

Orlando, USA

Congreso; 29 Reunión Anual de la American Society for Reproductive Immunology (ASRI).; 2009

Sociedad Americana de Inmunologia Reproductiva

PCOS is an endocrine disease that affects 7% of premenopausal women and is a major cause of subfertility. PCOS can be diagnosed by hyperandrogenism, oligo-anovulation and/or polycystic ovaries and is often associated to diabetes, obesity and metabolic syndrome. A chronic low-grade inflammation is present and has been postulated to play a central role in the pathomorphology of PCOS. Animal models with PCOS-like symptoms are largely restricted to rats, and hence, provide only limited insights on the role of the immune system. Thus, we aimed to develop a mouse model which mirrors key features of PCOS in humans. We administered dehydroepiandrosterone (DHEA) or vehicle (control) for various durations and at different ages and identified that injection of 60 mg DHEA/kg body weight (BW) for 20 consecutive days to Balb/c females starting at 23 days of age resulted in PCOS-like symptoms, such as ovarian cysts, estrous cycle arrest, increased serum estradiol levels (ELISA) and BW. Immunohistochemistry analyses of ovarian sections from these mice revealed an intense expression of vascular cell adhesion molecule (VCAM)-1 in the follicles and cysts [enlarged follicles with compact granulosa cell layer (GCL)]. The majority of the cyst also revealed cell infiltration, especially in the GCL, which could be identified as intercellular adhesion molecule (ICAM)-1+, MHCII+ or CD4+. In ovaries of shaminjected mice, expression of these markers were virtually absent in antral follicles. Flow cytometric analyses of peripheral blood cells revealed an increased frequency of CD4+CD25+ T cells and CD4+CD49b+ NKT cells in DHEA-treated mice, along with a inflammatory cytokine surge by stimulated peritoneal cells. These results confirm the successful design to generate a mouse model with PCOS-like symptoms and allowed to identify profound alterations of the immune response in PCOS, such as VCAM-1 up-regulation. This could provide a therapeutic target and a rationale for the cyst formation and anovulation.