Bisphenol A Impairs Androgen Receptor Pathway and Prostate Development

Endocrine Disruptor Chemicals (EDCs) are emerging environmental contaminants widely used in domestic, agricultural, and personal-care products to enhance their performance. Their persistence in different environmental matrices and their ability to bioaccumulate have raised major concerns about continuous human exposure, even at low doses, through ingestion or skin contact. Among these compounds, Bisphenol A (BPA) has gained particular attention due to its structural similarity to steroid hormones and its ability to interfere with the endocrine system. Increasing evidence suggests that BPA adversely affects the male reproductive system, especially the prostate gland that appears sensitive to its activity. In this study, we showed preliminary data comparing the actions of BPA and the endogenous hormone Dihydrotestosterone (DHT) on 2D and 3D human prostate cell cultures. MTT and cell proliferation assays were performed to identify the concentration ranges of BPA and DHT that significantly influenced cell physiology. Protein expression of Proliferating Cell Nuclear Antigen (PCNA) was analyzed by Western blot, while Androgen Receptor (AR) localization after BPA exposure was examined by immunofluorescence. Our results showed that BPA exerted an inhibitory effect on both culture models. In 2D cultures, BPA caused AR retention in the cytoplasm, leading to a reduction in cellular proliferation. Moreover, the proliferative effect of DHT decreased when cells were co-treated with DHT and BPA, suggesting that BPA interferes with AR nuclear translocation and hormone responsiveness. In 3D prostate organoid (PO) cultures, DHT played a crucial role in PO maturation. Conversely, BPA did not replace DHT activity, but it showed its antiandrogenic activity when the PO was treated by BPA+DHT that resulted in smaller, less developed organoids, confirming BPA’s interference with DHT-driven morphogenesis. Overall, our findings indicated that BPA interfered with androgenic pathways acting as an antiandrogenic compound, ultimately impairing normal prostate development.