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BDE-209 inhibits pluripotent genes expression and induces apoptosis in human embryonic stem cells.
- Source :
-
Journal of applied toxicology : JAT [J Appl Toxicol] 2016 May; Vol. 36 (5), pp. 659-68. Date of Electronic Publication: 2015 Jul 23. - Publication Year :
- 2016
-
Abstract
- Decabromodiphenyl ether (BDE-209) has been detected in human serum, semen, placenta, cord blood and milk worldwide. However, little is known regarding the potential effects on the early human embryonic development of BDE-209. In this study, human embryonic stem cell lines FY-hES-10 and FY-hES-26 were used to evaluate the potential effects and explore the toxification mechanisms using low-level BDE-209 exposure. Our data showed that BDE-209 exposure (1, 10 and 100 nM) reduced the expression of pluripotent genes such as OCT4, SOX2 and NANOG and induced human embryonic stem cells (hESCs) apoptosis. The downregulation of BIRC5/BCL2 and upregulation of BAX were related to apoptosis of hESCs induced by BDE-209 exposure. A mechanism study showed that OCT4 down-regulation accompanied by OCT4 promoter hypermethylation and increasing miR-145/miR-335 levels, OCT4 inhibitors. Moreover, BDE-209 could increase the generation of intracellular reactive oxygen species (ROS) and decrease SOD2 expression. The ROS increase and OCT4 downregulation after BDE-209 exposure could be reversed partly by antioxidant N-acetylcysteine supplement. These findings showed that BDE-209 exposure could decrease pluripotent genes expression via epigenetic regulation and induce apoptosis through ROS generation in human embryonic stem cells in vitro.<br /> (Copyright © 2015 John Wiley & Sons, Ltd.)
- Subjects :
- Acetylcysteine pharmacology
Apoptosis drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Down-Regulation
Epigenesis, Genetic
Human Embryonic Stem Cells metabolism
Humans
Inhibitor of Apoptosis Proteins genetics
Inhibitor of Apoptosis Proteins metabolism
MicroRNAs genetics
MicroRNAs metabolism
Nanog Homeobox Protein genetics
Nanog Homeobox Protein metabolism
Octamer Transcription Factor-3 genetics
Octamer Transcription Factor-3 metabolism
Pluripotent Stem Cells metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species metabolism
SOXB1 Transcription Factors genetics
SOXB1 Transcription Factors metabolism
Superoxide Dismutase genetics
Superoxide Dismutase metabolism
Survivin
Up-Regulation
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Halogenated Diphenyl Ethers toxicity
Human Embryonic Stem Cells drug effects
Pluripotent Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1263
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of applied toxicology : JAT
- Publication Type :
- Academic Journal
- Accession number :
- 26206603
- Full Text :
- https://doi.org/10.1002/jat.3195