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Bisphenol A (BPA) induces progesterone receptor expression in an estrogen receptor α-dependent manner in perinatal brain.
Neurotoxicology and Teratology ( IF 2.6 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.ntt.2020.106864
Allyssa Fahrenkopf 1 , Christine K Wagner 1
Affiliation  

Bisphenol A (BPA) is a xenoestrogen that is prevalent in the environment of industrialized nations due its use in the production of many plastic household items. Virtually all adults in the U.S. have detectable levels of BPA in urine and it can be measured in fetal serum and in breastmilk, making developmental exposure a particular concern. The present study utilizes a progesterone receptor (PR) expression bioassay to assess the estrogen receptor α (ERα)-dependent effects of BPA in fetal rodent brain following maternal exposure. Maternal ingestion of 10 μg/kg/day, but not 50 μg/kg/day, BPA from gestational day 14-22 significantly increased levels of PR immunoreactivity (PRir) in the medial preoptic nucleus (MPN) of female offspring. PR expression in the perinatal MPN is highly dependent on the activation of ERα, but not ERβ, by estrogens. Indeed, injections of BPA (5 μg/kg) to neonates from postnatal day 2-4 (P2-4) significantly increased PR expression in the MPN of postnatal day 5 females compared to the MPN of females administered the oil vehicle. However, pretreatment with the ER antagonist, ICI 182,780 from P1-4 significantly attenuated the effects of BPA on PR expression, indicating an ERα-dependent mechanism. The present results also demonstrate a non-monotonic effect of BPA on the direct expression of a transcription factor in developing brain.

中文翻译:

双酚A(BPA)在围产期大脑中以雌激素受体α依赖性方式诱导孕激素受体表达。

双酚A(BPA)是一种异雌激素,由于在许多塑料日用品的生产中使用,因此在工业化国家的环境中很普遍。几乎在美国,所有成年人的尿液中都有BPA的可检测水平,并且可以在胎儿血清和母乳中对其进行测量,因此特别关注发育暴露。本研究利用孕激素受体(PR)表达生物测定法评估母体暴露后胎儿啮齿动物脑中BPA的雌激素受体α(ERα)依赖性效应。孕妇在妊娠第14-22天摄入10μg/ kg /天,而不是50μg/ kg /天的BPA会显着提高雌性子孙后内侧内侧核(MPN)中PR免疫反应性(PRir)的水平。围产期MPN中的PR表达高度依赖于雌激素对ERα的激活,而与ERβ无关。确实,与使用油剂的女性MPN相比,出生后2-4天(P2-4)的新生儿注射BPA(5μg/ kg)显着提高了出生后5天女性的MPN中PR表达。但是,用P1-4的ER拮抗剂ICI 182,780进行的预处理显着减弱了BPA对PR表达的影响,表明了ERα依赖性机制。本结果还证明了BPA对发育中的大脑中转录因子直接表达的非单调作用。表示依赖于ERα的机制。本结果还证明了BPA对发育中的大脑中转录因子直接表达的非单调作用。表示依赖于ERα的机制。本结果还证明了BPA对发育中的大脑中转录因子直接表达的非单调作用。
更新日期:2020-03-30
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