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戊酸雌二醇对新生大鼠卵巢雄激素受体和抗缪勒管激素的重编程导致多囊卵巢表型。

Neonatal exposure to estradiol valerate reprograms the rat ovary androgen receptor and anti-Müllerian hormone to a polycystic ovary phenotype.

机构信息

Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago, Chile; Faculty of Sciences, Universidad de Valparaiso, 2360102, Valparaiso, Chile.

Laboratory of Neurobiochemistry, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, 8380492 Independencia, Santiago, Chile.

出版信息

Reprod Toxicol. 2018 Jan;75:127-135. doi: 10.1016/j.reprotox.2017.10.005. Epub 2017 Oct 18.

Abstract

To understand the impact of exposure to steroids in the early step of ovary development (a stage occurring in uterus in humans), we studied neonatal exposure to estradiol valerate (EV) in rats regarding polycystic ovary (PCO) development as well as expression of androgen receptor (Ar) and anti-Müllerian hormone (AMH), a marker of ovarian follicular development. Rats exposed to one dose of EV (10mg/kg, sc) during their first 12h of life were euthanized at 2, 30 and 60days of age. Gene array and real-time PCR studies showed Ar and AMH up regulation in the ovary at 2days of age and persisted at 60days of age, when a PCO phenotype was evident with increased levels of Ar and AMH proteins. The single neonatal exposure in rats suggests participation of EV in developing PCO syndrome. Its persistence also suggests that estradiol reprograms ovarian function and disease during adulthood.

摘要

为了了解在卵巢发育早期(人类在子宫中发生的阶段)暴露于类固醇的影响,我们研究了新生大鼠暴露于戊酸雌二醇(EV)对多囊卵巢(PCO)发育以及雄激素受体(Ar)和抗缪勒管激素(AMH)表达的影响,后者是卵巢卵泡发育的标志物。在生命的头 12 小时内接受一次 EV(10mg/kg,sc)处理的大鼠在 2、30 和 60 天龄时被安乐死。基因阵列和实时 PCR 研究表明,在 2 天龄时卵巢中 Ar 和 AMH 的表达上调,并持续到 60 天龄时,此时出现 PCO 表型,Ar 和 AMH 蛋白水平升高。大鼠的单次新生期暴露表明 EV 参与了 PCO 综合征的发生。其持续存在也表明雌二醇在成年期重新编程卵巢功能和疾病。

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