The aim of this study was to investigate uterine lesions, uterine endocrine status and expression of genes involved in uterine differentiation in a rat model of polycystic ovary syndrome (PCOS). The possible involvement of the androgen receptor (AR) was also investigated. PCOS rats showed an increased incidence of uterine epithelial and glandular lesions and elevated serum testosterone level, which was not detected in uterine tissue. Uterine 17β-estradiol, estrone and progesterone were detected in 100%, 75% and 50% of the animals, respectively. This was associated with a decrease in and an increase in , and , suggesting that uterine steroids are not synthesized in PCOS and that alterations in these enzymes may explain the absence of testosterone and low progesterone. In addition, ESR2 decreased and AR increased, suggesting possible steroid receptor crosstalk. Genes associated with uterine differentiation, PTEN and WNT5a, also showed reduced expression. PCOS rats treated with flutamide, an AR antagonist, were similar to PCOS rats in terms of uterine lesions, serum steroid levels, ESR2, PTEN and WNT5a expression. However, testosterone, AR and aromatase levels were similar to control rats, with decreased expression of ESR1 and HOXA10, suggesting that these expressions are AR dependent. Our results suggest that the primary cause of the observed uterine lesions in the PCOS rat model is the altered endocrine status and consequently changes in genes related to uterine differentiation.

中文翻译：

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多囊卵巢综合征大鼠模型的子宫组织病理学和类固醇代谢

本研究的目的是探讨多囊卵巢综合征（PCOS）大鼠模型的子宫病变、子宫内分泌状态以及参与子宫分化的基因表达。还研究了雄激素受体（AR）可能的参与。 PCOS 大鼠子宫上皮和腺体病变发生率增加，血清睾酮水平升高，但在子宫组织中未检测到。 100%、75% 和 50% 的动物体内检测到子宫 17β-雌二醇、雌酮和孕酮。这与 、 和 的减少和增加有关，表明多囊卵巢综合征中不合成子宫类固醇，并且这些酶的改变可以解释睾酮缺乏和黄体酮低的原因。此外，ESR2 降低且 AR 增加，表明可能存在类固醇受体串扰。与子宫分化相关的基因 PTEN 和 WNT5a 也表现出表达减少。用 AR 拮抗剂氟他胺治疗的 PCOS 大鼠在子宫病变、血清类固醇水平、ESR2、PTEN 和 WNT5a 表达方面与 PCOS 大鼠相似。然而，睾酮、AR 和芳香酶水平与对照大鼠相似，ESR1 和 HOXA10 表达降低，表明这些表达是 AR 依赖性的。我们的结果表明，在 PCOS 大鼠模型中观察到的子宫病变的主要原因是内分泌状态的改变以及因此与子宫分化相关的基因的变化。