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低剂量双酚 A 的经口暴露促进老龄大鼠外侧前列腺的增殖,并诱导上皮-间充质转化。

Oral exposure of low-dose bisphenol A promotes proliferation of dorsolateral prostate and induces epithelial-mesenchymal transition in aged rats.

机构信息

National Evaluation Centre for the Toxicology of Fertility Regulating Drugs, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China.

Reproductive and developmental research institute of Fudan university, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, China.

出版信息

Sci Rep. 2018 Jan 11;8(1):490. doi: 10.1038/s41598-017-18869-8.

Abstract

Bisphenol A (BPA) is a well-known endocrine disruptor compound reported to have prostate toxicity. This study aimed to assess the effect of BPA on the proliferation of dorsolateral prostate (DLP) and the expression of epithelial-mesenchymal transition (EMT)-related genes in aged rats. Male aged SD rats were treated with BPA (10.0, 30.0, and 90.0 µg/kg i.g., daily) or vehicle (i.g., daily) for 3 months. Treatment with BPA resulted in increased the expression of PCNA, DLP weight and DLP epithelial height compared with the control group (P < 0.01); such effects were more obvious at higher BPA doses. 90 µg/kg BPA significantly increased the estrogen to androgen ratio (P < 0.05). The EMT chip showed the BPA induced upregulation of vimentin, Snail, Twist1, and transforming growth factor beta 1, as well as the downregulation of E-cadherin in the DLP. Immunohistochemical data showed that the expression of vimentin, estrogen receptor subtypes, and androgen receptor increased and the expression of E-cadherin decreased in 30 and 90 µg/kg BPA groups. It was concluded that environmental exposure to low doses of BPA might promote the proliferation of DLP in aged rats by increasing the estrogen to androgen ratio and inducing EMT.

摘要

双酚 A(BPA)是一种众所周知的内分泌干扰化合物,据报道具有前列腺毒性。本研究旨在评估 BPA 对老年大鼠背外侧前列腺(DLP)增殖和上皮-间充质转化(EMT)相关基因表达的影响。雄性老年 SD 大鼠每天经口给予 BPA(10.0、30.0 和 90.0μg/kg)或载体(每天)处理 3 个月。与对照组相比,BPA 处理组 PCNA、DLP 重量和 DLP 上皮高度的表达增加(P<0.01);在较高 BPA 剂量下,这种作用更为明显。90μg/kg BPA 显著增加了雌激素与雄激素的比值(P<0.05)。EMT 芯片显示 BPA 诱导 DLP 中波形蛋白、Snail、Twist1 和转化生长因子β1 的上调,以及 E-钙黏蛋白的下调。免疫组织化学数据显示,30 和 90μg/kg BPA 组中波形蛋白、雌激素受体亚型和雄激素受体的表达增加,E-钙黏蛋白的表达减少。结论:环境暴露于低剂量 BPA 可能通过增加雌激素与雄激素的比值并诱导 EMT 来促进老年大鼠 DLP 的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43fc/5764998/b37735b20b60/41598_2017_18869_Fig1_HTML.jpg

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