Effects of prepubertal exposure to androgens on histofunctional development of the rat uterus

BRACHO GS; WAIGANDT C; ALTAMIRANO GA; KASS L; MUÑOZ-DE-TORO M; LUQUE EH; BOSQUIAZZO VL

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Thepolycystic ovary syndrome (PCOS) is a disease that can affect women in thereproductive age. It is characterized for anovulation, hyperandrogenism andpolycystic ovaries. PCOS is associated with an increased risk of endometrialcancer and fertility problems. This study was performed to evaluate the effectsof hyperandrogenism on the histofunctional development of the rat uterus. Toinduce PCOS, Wistar rats were injected sc with sesame oil (control group) orDehydroepiandrosterone (DHEA, 6 mg/100 g body weight) from postnatal day 21(PND21) to PND41. Before sacrifice, the animals received an ip injection ofBromodeoxyuridine (BrdU, 6mg/100 g body weight). The uterine horns weredissected and included in paraffin. The thickness of the subepithelial andmyometrial stroma, as well as, the density of the uterine glands and the nucleidensity of the subepithelial and stromal compartments were evaluated in thehistological sections. BrdU incorporation and androgen receptor (AR) expressionwere also quantified in all uterine compartments. The DHEA group showed an incrementin the subepithelial (control: 153.3±10.4um vs DHEA: 238.3±24.7um; p<0.05)and myometrial (control: 149.6±10.4um vs DHEA: 292.3±17.9um; p < 0.05)thickness, and in the uterine gland density (control: 2.0±0.2vs DHEA: 2.6±0.2;p<0.05). On the other hand, the nuclei density in both compartments wasdecreased in DHEA animals compared to control rats. The proliferation of thesubepithelial stroma was higher in the DHEA than in control animals (control:1.56±0.5% vs DHEA: 7.3±2.1%; p<0.05). Also, DHEA induces the expression ofAR in the cytoplasm of luminal and glandular epithelial cells and in the nucleiof the subepithelial and myometrial stroma. The present study provides evidencethat DHEA treatment induce changes in uterine histomorphology and steroidreceptor expression that could have long-time consequences on fertility and/oruterine anomalies.