Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Departamento de Química General e Inorgánica, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
Instituto de Salud y Ambiente del Litoral (ISAL, UNL-CONICET), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
Mol Cell Endocrinol. 2024 May 1;585:112198. doi: 10.1016/j.mce.2024.112198. Epub 2024 Mar 11.
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 Star and an increase in Hsd17b2, Srd5a1 and Cyp19a1, suggesting that uterine steroids are not synthesized de novo 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.
本研究旨在探讨多囊卵巢综合征（PCOS）大鼠模型中子宫病变、子宫内分泌状态以及涉及子宫分化的基因表达情况，同时也研究了雄激素受体（AR）的可能参与情况。PCOS 大鼠表现出较高的子宫上皮和腺体病变发生率以及血清睾丸酮水平升高，但在子宫组织中未检测到。100%、75%和 50%的动物分别检测到了子宫 17β-雌二醇、雌酮和孕酮。这与 Star 的减少和 Hsd17b2、Srd5a1 和 Cyp19a1 的增加有关，表明 PCOS 中子宫类固醇并非从头合成，这些酶的改变可能解释了缺乏睾丸酮和低孕酮的原因。此外，ESR2 减少而 AR 增加，表明可能存在类固醇受体相互作用。与子宫分化相关的基因，如 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，睾丸酮、AR 和芳香化酶水平与对照组大鼠相似，ESR1 和 HOXA10 的表达减少，表明这些表达依赖于 AR。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，进而导致与子宫分化相关的基因发生变化。
