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

Reprod Toxicol. 2016 Oct:65:382-393. doi: 10.1016/j.reprotox.2016.09.001. Epub 2016 Sep 7.

Abstract

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.

Keywords: Atrazine; Bisphenol a; Developmental origins of disease; Endocrine disruptor; Gene-environment interaction; Nuclear programming; Obesogen; Perfluorooctanoic acid; Phthalate; Transcriptome; Tributyltin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrazine / toxicity
  • Benzhydryl Compounds / toxicity
  • Caprylates / toxicity
  • Cell Death / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Survival / genetics
  • Diethylhexyl Phthalate / toxicity
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / metabolism
  • Endocrine Disruptors / toxicity*
  • Fluorocarbons / toxicity
  • Gene Expression Regulation, Developmental / drug effects*
  • Macaca mulatta
  • Phenols / toxicity
  • Transcriptome / drug effects
  • Trialkyltin Compounds / toxicity

Substances

  • Benzhydryl Compounds
  • Caprylates
  • Endocrine Disruptors
  • Fluorocarbons
  • Phenols
  • Trialkyltin Compounds
  • tributyltin
  • perfluorooctanoic acid
  • Diethylhexyl Phthalate
  • bisphenol A
  • Atrazine