Impacts of androgen modulation on the male prostate after perinatal exposure to the endocrine disruptor bisphenol A

Abstract

Prostate cancer is the most common neoplasia among men in the world. It is a complex pathology, highly sensitive and responsive to the steroid hormones action, just like the normal prostate, which depends on their action for its development and homeostasis. In this scenario, it is notable that disturbances in the hormone levels, through their own receptors (AR, ER± and ER²), lead to pre-malignant lesions and even prostate cancer. Since the modulation of the hormones levels is relevant, a disrupted scenario induced by endocrine disruptors (EDCs), such as bisphenol A (BPA), is a concern for several researchers due to their direct impacts on hormonal regulation. Thus, the present study aims to evaluate the responses under different conditions of androgenic modulation in the ventral prostate of male Mongolian gerbils (Meriones unguiculatus) exposed during the perinatal period to BPA (50 µg/kg/day). The animals were randomly divided into six experimental groups: a control group (Intact Control) and five exposed to BPA in the perinatal period, four others (except group BPA) subjected to treatments to promote different androgenic scenarios (Testosterone, Surgical Castration, Chemical Castration and Vehicle). At twelve months of age, the animals will be euthanized to collect ventral prostate samples. The samples will be used for histopathological, immunohistochemical and molecular analyses. The expression of AR, ER±, and ER², will be evaluated and associated with control and cell death in the epithelium, epithelial lesions, and stroma. The study therefore aims to elucidate and characterize the expression of hormone receptors, the incidence and quantity of lesions in different treatments and infer possible associations between androgen modulation and neoplastic development.