Oral administration of low-dose bisphenol A promotes proliferation of ventral prostate and upregulates prostaglandin D2 synthase expression in adult rats

This study aims to assess the effect of low oral dose of bisphenol A (BPA) on proliferation of ventral prostate (VP) and expression of related genes in adult rats. Three-month-old male Sprague Dawley rats were treated daily with BPA (10, 30, or 90 µg/kg, per os), 17β-estradiol (E2, 10.0 µg/kg, subcutaneously), or vehicle for 4 weeks. Treatment with 10 µg/kg BPA resulted in increased animal weight and VP epithelial height compared with the controls (p < 0.01), while such effects were less pronounced in higher BPA doses. Treatment with E2 showed opposite effects, with significantly decreased animal weight and VP epithelial height (p < 0.01). Interestingly, BPA increased serum E2 and reduced testosterone levels and significantly increased the estrogen to androgen ratio (p < 0.05). In addition, BPA slightly increased dihydrotestosterone (DHT) levels. Immunohistochemistry data showed that BPA significantly upregulated proliferating cell nuclear antigen expression (p < 0.01). Furthermore, microarray and reverse transcription polymerase chain reaction analyses showed that BPA induced upregulation of prostaglandin D2 synthase (Ptgds), Fas, Pbef1, and complement factor B (Cfb)as well as downregulation of Pttg1 and Fabp4 in the VP. These results indicated that environmental exposure to low doses of BPA may induce proliferation of VP in adult rats by increasing the estrogen to androgen ratio and upregulating expression of Ptgds to promote production of DHT.