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

Ludivine Renaud; Matthew Huff; Willian A da Silveira; Mila Angert; Martin Haas; Gary Hardiman

doi:10.2174/1389202920666190603123040

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

Curr Genomics. 2019 May;20(4):260-274. doi: 10.2174/1389202920666190603123040.

Authors

Ludivine Renaud¹, Matthew Huff¹, Willian A da Silveira¹, Mila Angert¹, Martin Haas¹, Gary Hardiman¹

Affiliation

¹ 1Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; 2MUSC Bioinformatics, Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, USA; 3MS in Biomedical Sciences Program, Medical University of South Carolina, Charleston, SC, USA; 4School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, BelfastBT9 5AG, UK; 5Department of Medicine, University of California, La Jolla, CA, USA; 6Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, CA, USA; 7Division of Biological Sciences, University of California San Diego, La Jolla, California, CA, USA.

Abstract

Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wild-life 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 dis-rupt 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.

Keywords: Endocrine disruptor (ED); bisphenol-A (BPA); epigenomic biomarkers; meta-analysis; microarray; prostate epithelial cells; xenoestrogen (XE).