Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells

Abstract

: Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wildlife and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and disrupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study. Methodology: In this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray. Results: Exposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes). Conclusion: We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.

Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease

“…A whole-genome microarray performed in healthy primary human prostate epithelial cells has shown that BPA treatment affects the expression of genes relevant for cancer development and progression in prostate cells, involved in pathways modulating angiogenesis, cell proliferation, cell cycle, DNA replication and repair, metabolism, inflammation, and immune response pathways. In parallel, BPA deregulates the expression of transcripts relevant to epigenetic changes, such as histone and DNA methylation modifying enzymes [167]. Similar results have been obtained by Fatma Karaman et al who performed PCR arrays in the human prostate adenocarcinoma PC-3 cell line to investigate the transcriptional profiling of chromatin-modifying enzymes and DNA methylation levels of tumor suppressor genes including p16, Cyclin D2, and Rassf1.…”

BPA-induced prostatic hyperplasia in vitro is correlated with the unbalanced gene expression of AR and ER in the epithelium and stroma

“…Prostate is an effector organ of hormones, and hormone receptors are indispensable for its normal development and metabolism. Low-level BPA, comparable to those routinely detected in the environment, critically affects global transcriptomic responses in prostate epithelial cells through cross-regulation of the signaling networks (Renaud et al, 2019). Potential effects for prostate gland are further compounded by the BPA-associated changes of androgen-signaling pathway and estrogen-signaling pathway.…”

How microplastic components influence the immune system and impact on children health: Focus on cancer

“…BPA exposure of newborn rats resulted in the modulation of the methylation of promoter regions of genes related to embryonic SC pluripotency, cell-tocell signaling and interaction, cell-mediated immune response, cellular growth and proliferation, nucleic acid metabolism, molecular transport, cellular assembly, and organization (Cheong et al, 2016). The epigenetic changes induced by BPA exposure have been corroborated not only in animal models but in vitro experiments, where this EDC also modified the epigenetic signature of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation in prostate epithelial cells (Renaud et al, 2019). In addition, this compound can also induce centrosomal abnormalities, microtubule nucleation, and anchorageindependent growth in prostate cancer cell lines (Tarapore et al, 2014).…”