title: BDE-209 inhibits pluripotent genes expression and induces apoptosis in human embryonic stem cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, People's Republic of, China.|Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, People's Republic of, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, People's Republic of, China.|Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, People's Republic of, China.
authors.forename: Dunjin
authors.initials: D
authors.lastname: Chen
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D000066449:Human Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000111:Acetylcysteine; D055768:Halogenated Diphenyl Ethers; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D055748:SOXB1 Transcription Factors; D013482:Superoxide Dismutase; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D000099156:Superoxide Dismutase 2; C494826:BAX protein, human; C000595707:BCL2 protein, human; C107489:BIRC5 protein, human; C541010:MIRN145 microRNA, human; C556347:MIRN335 microRNA, human; C486780:NANOG protein, human; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; C010902:decabromobiphenyl ether
keywords: BDE-209; apoptosis; hESCs; pluripotency and epigenetic