Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats.

Abstract

Prostate is sensitive to endocrine hormone level, and the synergetic effect of estrogen and androgen is critical in prostate growth. The change of signal pathways caused by the imbalance of estrogen and androgen might function in the occurrence of prostate diseases. As a well-known endocrine disruptor compound, bisphenol A (BPA) can disturb the normal function of endocrine hormone and affect prostate development. This study aims to investigate effects of BPA on the dorsolateral prostate (DLP) and the related gene expression of the tissue in adult Sprague-Dawley (SD) rats and to explore the mechanism for the effect of low-dose BPA on DLP hyperplasia. Three-month-old male SD rats were treated with BPA (10.0, 30.0, or 90.0 µg (kg.day)-1, gavage) or vehicle (gavage) for 4 weeks. BPA significantly increased the DLP weight, the DLP organ coefficient, and the prostate epithelium height (p < 0.01) of rats dose-dependently. Microarray analysis and quantitative real-time polymerase chain reaction showed that BPA significantly upregulated the transcriptional levels of some genes, including pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp1, and Pcna. Furthermore, the expression of PCNA (p < 0.01), androgen receptor (p < 0.01), and EGF receptor (EGFR) (p < 0.001) in DLP was increased significantly by BPA treatment, and the expression of estrogen receptor alpha was also upregulated. The findings evidenced that low-dose BPA could induce DLP hyperplasia in adult rats, and the upregulated EGF/EGFR pathway that was responsive to estrogen and androgen might play an essential role in the DLP hyperplasia induced by low-dose BPA.