Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many of which are traceable to effects on stem cell programming underlying organismal development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five different EDCs for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. EDCs tested included bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP). We observed little effect of BPA, and small numbers of affected genes (119 or fewer) with the other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes, activation of cell death genes, suppression of genes downstream of several stress response mediators, and modulations in several genes that regulate pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed. Overall design: Effects of chronic exposure to low concentrations of 5 EDCs were tested in rhesus monkey embryonic stem cells