CONICET | Buscador de Institutos y Recursos Humanos

The present study investigated the role of metformin in preventing adverse effects produced by hyperandrogenism on uterine function. Daily injection of dehydroepiandrosterone (DHEA) for 20 consecutive days induces polycystic ovaries in BALB/c mice. We found that DHEA produced alterations on uterine histology closely related to the development of tumor structures concomitantly with increased incidence of uterine apoptosis. DHEA also induced a pro-inflammatory status represented by increased prostaglandin (PG) F2 alpha levels and uterine cyclooxygenase (COX) 2 abudance and diminished levels of PGE. On the other hand, DHEA also induced a pro-oxidant status since it increased nitric oxide synthase (NOS) activity and decreased superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) levels. DHEA also induced the increase of CD4+ and the decrease of CD8+ T lymphocyte percentages infiltrating uterine tissue. When metformin was administered together with DHEA uterine histology and apoptosis did not differ when compared with controls. Metformin prevented the pro-inflammatory condition generated by DHEA given that uterine PGF2 alpha, COX2 abundance and NOS activity were similar to those observed in controls. In addition, metformin had no effect in preventing the adverse effect of DHEA in the anti-oxidant parameters evaluated; SOD and CAT activities and GSH content. Therefore, metformin lead the percentages of CD4+ and CD8+ T populations infiltrating uterine tissue to those observed in controls. We conclude that metformin is able to restore direct or indirectly uterine function by avoiding some inflammatory and oxidative alterations produced by hyperandrogenism. (Supported in part by ANPCyT grants PICTR 32529 and PICT 949).