TY - JOUR
T1 - Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells
AU - Midic, Uros
AU - Vincent, Kailey A.
AU - VandeVoort, Catherine A.
AU - Latham, Keith E.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 28 days, 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.
AB - 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 28 days, 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.
KW - Atrazine
KW - Bisphenol a
KW - Developmental origins of disease
KW - Endocrine disruptor
KW - Gene-environment interaction
KW - Nuclear programming
KW - Obesogen
KW - Perfluorooctanoic acid
KW - Phthalate
KW - Transcriptome
KW - Tributyltin
UR - http://www.scopus.com/inward/record.url?scp=84987862420&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84987862420&partnerID=8YFLogxK
U2 - 10.1016/j.reprotox.2016.09.001
DO - 10.1016/j.reprotox.2016.09.001
M3 - Article
C2 - 27614199
AN - SCOPUS:84987862420
VL - 65
SP - 382
EP - 393
JO - Reproductigve Toxicoloy
JF - Reproductigve Toxicoloy
SN - 0890-6238
ER -