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

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.