Androgen receptor and uterine histoarchitecture in a PCOS rat model

BRACHO, GISELA S; ACOSTA MARIA V; ALTAMIRANO GABRIELA A; TSCHOPP MARIA V; LUQUE ENRIQUE H; KASS LAURA; BOSQUIAZZO VERÓNICA L

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2020

0303-7207

Polycystic ovary syndrome (PCOS) is associated withhyperandrogenemia and uterine abnormalities. Our aim was to investigatethe uterine effects of PCOS that are mediated through the androgenreceptor (AR). After weaning, female rats were treated with sesame oil(Control), dehydroepiandrosterone (DHEA), or DHEA + flutamide (FLU, an ARantagonist) for 20 consecutive days. On postnatal day 41, serum, ovarianand uterine tissues were collected. DHEA and DHEA+FLU rats showedincreased testosterone levels. DHEA rats showed increased epithelialheight, glandular density, subepithelial stroma and myometrial thickness,associated with decreased nuclei density. These rats also showedincreased uterine water content, with decreased aquaporin (AQP) 3, 7 and8 expression in the uterine epithelium and increased AQP8 expression inthe myometrium. DHEA rats also showed decreased uterine collagenremodeling, decreased cell proliferation in the subepithelial stroma, andincreased apoptosis in the luminal and glandular epithelium and in themyometrium. They also showed an increase in insulin-like growth factor-1and a decrease in phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase.The uterine stroma of DHEA rats showed no changes in progesteronereceptor or estrogen receptor alpha (ERα) and increased AR expression.DHEA+FLU rats showed a smaller increase in the myometrial thickness, anincrease in the uterine water content without AQP8 induction and asmaller decrease in collagen remodeling. These rats also showed noapoptosis induction and decreased proliferation in the myometrium,decreased ERα in the subepithelial stroma and myometrium and nomodifications in AR. Our results demonstrate that the uterine cellturnover and collagen remodeling in DHEA rats are regulated through AR,directly or indirectly associated with ERα expression.