Perinatal exposure to BPA leads to pronounced prostatic morphophysiological disorders in a rodent model of induced hyperplasia

Abstract

Bisphenol A (BPA) is a ubiquitous endocrine disruptor potentially harmful to male reproductive health. We aimed to investigate the impacts of perinatal exposure to a historically relevant and realistic dose of BPA on the ventral prostate under normal conditions and with prostatic hyperplasia in Mongolian gerbils (Meriones unguiculatus). Females were exposed to BPA (50 μg/kg/day) during gestation and lactation. The F1 male offspring were maintained until adulthood and subsequently treated with testosterone to induce prostatic hyperplasia. Morphological, molecular, and hormonal parameters were assessed on the ventral prostate. Testosterone-supplemented gerbils showed increased epithelium height and smooth muscle layer thickness. In the context of hyperplasia, perinatal exposure to BPA led to the onset of severe histopathologies (e.g., prostatic intraepithelial neoplasia, adenocarcinoma, and microacini), associated with increased cell proliferation. Perinatal BPA-exposed gerbils with prostatic hyperplasia showed increased pro-inflammatory markers (e.g., IL-6, COX-2, and F4/80), followed by a reduction in IL-10 protein levels. Regarding the steroid receptors, gerbils from this group presented a decrease in AR, followed by an increase in epithelial ERα expression. Molecularly, ERβ protein levels were higher in the prostate of perinatally exposed to BPA or testosterone-supplemented gerbils. Moreover, serum testosterone and estradiol levels increased after testosterone supplementation, whereas the T/E2 ratio increased in gerbils exposed to both treatments. Overall, the current study presents novel and comprehensive data on the life-long morphophysiological disorders caused by perinatal exposure to BPA on the ventral prostate of gerbils, highlighting the pronounced impacts observed in the context of hyperplasia.