Polycystic ovary syndrome (PCOS) is associated with hyperandrogenemia and uterine abnormalities. Our aim was to investigate the uterine effects of PCOS that are mediated through the androgen receptor (AR). After weaning, female rats were treated with sesame oil (Control), dehydroepiandrosterone (DHEA), or DHEA + flutamide (FLU, an AR antagonist) for 20 consecutive days. On postnatal day 41, serum, ovarian and uterine tissues were collected. DHEA and DHEA + FLU rats showed increased testosterone levels. DHEA rats showed increased epithelial height, glandular density, subepithelial stroma 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 expression in the myometrium. DHEA rats also showed decreased uterine collagen remodeling, decreased cell proliferation in the subepithelial stroma, and increased apoptosis in the luminal and glandular epithelium and in the myometrium. They also showed an increase in insulin-like growth factor-1 and a decrease in phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. The uterine stroma of DHEA rats showed no changes in progesterone receptor or estrogen receptor alpha (ERα) and increased AR expression. DHEA + FLU rats showed a smaller increase in the myometrial thickness, an increase in the uterine water content without AQP8 induction and a smaller decrease in collagen remodeling. These rats also showed no apoptosis induction and decreased proliferation in the myometrium, decreased ERα in the subepithelial stroma and myometrium and no modifications in AR. Our results demonstrate that the uterine cell turnover and collagen remodeling in DHEA rats are regulated through AR, directly or indirectly associated with ERα expression.

多囊卵巢综合征（PCOS）与高雄激素血症和子宫异常有关。我们的目的是研究通过雄激素受体（AR）介导的PCOS的子宫效应。断奶后，雌性大鼠连续20天接受麻油（对照），脱氢表雄酮（DHEA）或DHEA +氟他胺（FLU，AR拮抗剂）治疗。在出生后第41天，收集血清，卵巢和子宫组织。DHEA和DHEA + FLU大鼠的睾丸激素水平升高。DHEA大鼠表现出上皮高度，腺密度，上皮下基质和肌层厚度增加，与核密度降低有关。这些大鼠还显示出子宫含水量增加，子宫上皮中水通道蛋白（AQP）3、7和8的表达降低，子宫肌层中AQP8的表达增加。脱氢表雄酮（DHEA）大鼠还显示子宫胶原重构降低，上皮下基质的细胞增殖降低，以及管腔和腺上皮以及子宫内膜细胞凋亡增加。他们还显示出胰岛素样生长因子-1的增加和磷脂酰肌醇-3,4,5-三磷酸3-磷酸酶的减少。DHEA大鼠的子宫基质未显示孕激素受体或雌激素受体α（ERα）的变化，而AR表达增加。DHEA + FLU大鼠显示出子宫肌层厚度增加较小，子宫水含量增加而无AQP8诱导和胶原蛋白重构减少较小。这些大鼠还没有显示出凋亡诱导作用，并且在子宫肌层中的增殖减少，在上皮下基质和子宫肌层中的ERα降低，并且AR没有改变。