Effect of metformin treatment on uterine tissue in a murine model of prenatal hyperandrogenism

MARIA FLORENCIA HEBER; ALICIA BEATRIZ MOTTA; SILVANA FERREIRA; ALICIA ALEJANDRA GOYENECHE; GISELLE ADRIANA ABRUZZESE; CARLOS M TELLERIA

Chicago, USA

Congreso; ENDO 2018; 2018

Endocrine Society

Prenatal hyperandrogenism is hypothesized to be one of the main factors contributing tothe development of Polycystic Ovarian Syndrome (PCOS) in humans. PCOS is defined byoligo or anovulation, hyperandrogenism, and/or ovarian cysts. It is also associated withseveral conditions such as insulin resistance, metabolic syndrome, obesity, inflammationand infertility. Metformin (Met) is an insulin sensitizer commonly used to treat metabolicdisorders in PCOS. The aim of this work was to evaluate the effect of Met in the uterinetissue of prenatally hyperandrogenized (PH) rats. Pregnant Sprague-Dawley rats were s.c.injected with 1 mg of testosterone. A control (C) group was injected with vehicle(vegetable oil). The PH (N=120) and C (N=80) female offspring were phenotypicallycharacterized according to the estrous cycle as ovulatory or anovulatory by collectingvaginal smears from days 45 to 90. Twenty rats of each group received Met via oral (50mg/kg) from days 70 to 90. All animals were sacrificed at 90 days of life. We evaluated theeffect of Met in the estrous cycle, the uterine glandular density, the oxidative status, andthe protein levels of p-ERK1/2 and p-Akt. Our results showed that the C group has aregular estrous cycle. Within the PH group, 43?51% animals showed irregular estrouscycles (PHov), whereas 27?39% presented anovulatory cycles (PHanov). Met restored thecyclicity in 79% of the anovulatory animals (PHanov+Met) and in 63% of the ovulatoryirregular animals (PHov+Met). PH increased the endometrial glandular density (p