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 traceable to effects on stem cell programming underlying 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 EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed.
Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States.
Uros
U
Midic
Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States.
Kailey A
KA
Vincent
California National Primate Research Center and Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, United States.
Catherine A
CA
VandeVoort
Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States. Electronic address: lathamk1@msu.edu.
Keith E
KE
Latham
D000818:Animals; D001280:Atrazine / Q000633:toxicity; D001559:Benzhydryl Compounds / Q000633:toxicity; D002210:Caprylates / Q000633:toxicity; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008253:Macaca mulatta; D010636:Phenols / Q000633:toxicity; D059467:Transcriptome / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000633:toxicity; D000098826:Bisphenol A Compounds
D001280:Atrazine; D001559:Benzhydryl Compounds; D002210:Caprylates; D004051:Diethylhexyl Phthalate; D052244:Endocrine Disruptors; D005466:Fluorocarbons; D010636:Phenols; D014220:Trialkyltin Compounds; C011559:tributyltin; C023036:perfluorooctanoic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Atrazine; Bisphenol a; Developmental origins of disease; Endocrine disruptor; Gene-environment interaction; Nuclear programming; Obesogen; Perfluorooctanoic acid; Phthalate; Transcriptome; Tributyltin