Inhibition of androgen receptor and uterine histoarchitecture in a rat PCOS model

ALTAMIRANO GA; BOSQUIAZZO VL; ACOSTA MV; KASS L; BRACHO GS; LUQUE EH

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias-LXIV Reunión de la Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and uterine histoarchitecture modifications. The aim of this study was to investigate the uterine effects mediated by androgen receptor (AR) in a rat PCOS model. Beginning at weaning, female rats were injected sc with dehydroepiandrosterone (DHEA) 6mg/100g bw (PCOS) or DHEA 6mg/100g + flutamide (AR antagonist) 2mg/100g bw (PCOS+F) for 20 consecutive days. At postnatal day 41, serum and uterine tissues samples were collected. Similar testosterone, estradiol and progesterone serum levels and no estrous cyclicity were observed in both groups. The uterine water content was not modified between groups, although a decreased in AQP7-8 protein expression was found in PCOS+F rats. No differences in epithelial height, glandular density and subepithelial stroma thickness and nuclei density was observed between groups. However, the myometrium thickness was decreased in PCOS+F rats without changing the nuclei density. Also, in these animals an increase in the uterine collagen remodeling was observed. Cell apoptosis in the luminal epithelium was increased in PCOS+F rats, whereas cell proliferation in the subepithelial stroma and myometrium was decreased. Besides, in this group, insulin-like growth factor-I (IGF-1) mRNA expression was increased, whereas fosfatidilinositol-3,4,5-trisfosfato 3-fosfatasa (PTEN) expression was no modified in the stroma. Progesterone receptor expression was similar between groups, estrogen receptor 1 (ESR1) expression was reduced in the subepithelial stroma and myometrium, whereas AR expression was decreased in the subepithelial stroma of PCOS+F animals. The results demonstrated that uterine cell turnover and collagen remodeling found in the PCOS rats is regulated by AR, directly or indirectly through changes in ESR1 expression.