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

Uros Midic, Kailey A Vincent, Catherine A VandeVoort, Keith E Latham
Author Information
  1. Uros Midic: Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States.
  2. Kailey A Vincent: Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States.
  3. Catherine A VandeVoort: California National Primate Research Center and Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, United States.
  4. Keith E Latham: Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States. Electronic address: lathamk1@msu.edu.

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

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Grants

  1. P51 OD011107/NIH HHS
  2. R24 RR025880/NCRR NIH HHS
  3. P51 RR000169/NCRR NIH HHS
  4. R24 OD012221/NIH HHS
  5. R24 OD010967/NIH HHS

MeSH Term

Animals
Atrazine
Benzhydryl Compounds
Caprylates
Cell Death
Cell Differentiation
Cell Line
Cell Survival
Diethylhexyl Phthalate
Embryonic Stem Cells
Endocrine Disruptors
Fluorocarbons
Gene Expression Regulation, Developmental
Macaca mulatta
Phenols
Transcriptome
Trialkyltin Compounds

Chemicals

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