Ludivine Renaud, Matthew Huff, Mila Angert, Willian A. da Silveira, Martin Haas and Gary Hardiman* Pages 1 - 14 ( 14 )
Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wildlife and human health. Two important EDCs are the synthetic estrogen 17a-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 recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study. 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. 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). 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.
Endocrine disruptor (ED), xenoestrogen (XE), bisphenol-A (BPA), microarray, prostate epithelial cells, meta-analyis, epigenomic biomarkers
Department of Medicine, Medical University of South Carolina, Charleston, SC, MUSC Bioinformatics, Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, Department of Medicine, University of California, La Jolla, CA, MUSC Bioinformatics, Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, Belfast BT9 5AG