Androgen receptor and uterine histoarchitecture in a PCOS rat model

Abstract

Polycysticovary syndrome (PCOS) is associated with hyperandrogenemia and uterine abnormalities.Our aim was to investigate the uterine effects of PCOS that are mediated throughthe androgen receptor (AR). After weaning, female rats were treated with sesameoil (Control), dehydroepiandrosterone (DHEA), or DHEA + flutamide (FLU, an ARantagonist) for 20 consecutive days. On postnatal day 41, serum, ovarian and uterinetissues were collected. DHEA and DHEA+FLU rats showed increased testosteronelevels. DHEA rats showed increased epithelial height, glandular density, subepithelialstroma and myometrial thickness, associated with decreased nuclei density.These rats also showed increased uterine water content, with decreased aquaporin(AQP) 3, 7 and 8 expression in the uterine epithelium and increased AQP8 expressionin the myometrium. DHEA rats also showed decreased uterine collagen remodeling,decreased cell proliferation in the subepithelial stroma, and increased apoptosisin the luminal and glandular epithelium and in the myometrium. They also showedan increase in insulin-like growth factor-1 and a decrease in phosphatidylinositol-3,4,5-trisphosphate3-phosphatase. The uterine stroma of DHEA rats showed no changes inprogesterone receptor or estrogen receptor alpha (ERα) and increased AR expression. DHEA+FLU ratsshowed a smaller increase in the myometrial thickness, an increase in theuterine water content without AQP8 induction and a smaller decrease in collagenremodeling. These rats also showed no apoptosis induction and decreasedproliferation in the myometrium, decreased ERα in the subepithelial stroma and myometrium andno modifications in AR. Our results demonstrate that the uterine cell turnoverand collagen remodeling in DHEA rats are regulated through AR, directly orindirectly associated with ERα expression.