PMID- 34607665 OWN - NLM STAT- MEDLINE DCOM- 20211006 LR - 20211006 IS - 1001-0742 (Print) IS - 1001-0742 (Linking) VI - 109 DP - 2021 Nov TI - DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell development in GC-2spd. PG - 161-170 LID - S1001-0742(21)00134-0 [pii] LID - 10.1016/j.jes.2021.04.001 [doi] AB - Decabrominated diphenyl ether (BDE-209) is generally utilized in multiple polymer materials as common brominated flame retardant. BDE-209 has been listed as persistent organic pollutants (POPs), which was considered to be reproductive toxin in the environment. But it still remains unclear about the effects of BDE-209 on DNA methylation and the induced-male reproductive toxicity. Due to the extensive epigenetic regulation in germ line development, we hypothesize that BDE-209 exposure impacts the statue of DNA methylation in spermatocytes in vitro. Therefore, the mouse GC-2spd (GC-2) cells were used for the genome wide DNA methylation analysis after treated with 32 mug/mL BDE-209 for 24 hr. The results showed that BDE-209 caused genomic methylation changes with 32,083 differentially methylated CpGs in GC-2 cells, including 16,164 (50.38%) hypermethylated and 15,919 (49.62%) hypomethylated sites. With integrated analysis of DNA methylation data and functional enrichment, we found that BDE-209 might affect the functional transcription in cell growth and sperm development by differential gene methylation. qRT-PCR validation demonstrated the involvement of p53-dependent DNA damage response in the GC-2 cells after BDE-209 exposure. In general, our findings indicated that BDE-209-induced genome wide methylation changes could be interrelated with reproductive dysfunction. This study might provide new insights into the mechanisms of male reproductive toxicity under the environmental exposure to BDE-209. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Li, Xiangyang AU - Li X AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. FAU - Zhang, Yue AU - Zhang Y AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. FAU - Dong, Xiaomin AU - Dong X AD - Experimental Center for basic medical teaching, Basic Medical Sciences, Capital Medical University, Beijing 100069, China. FAU - Zhou, Guiqing AU - Zhou G AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. FAU - Sang, Yujian AU - Sang Y AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. FAU - Gao, Leqiang AU - Gao L AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. FAU - Zhou, Xianqing AU - Zhou X AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: xqzhou2@163.com. FAU - Sun, Zhiwei AU - Sun Z AD - Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. LA - eng PT - Journal Article DEP - 20210424 PL - Netherlands TA - J Environ Sci (China) JT - Journal of environmental sciences (China) JID - 100967627 RN - 0 (Flame Retardants) RN - 0 (Halogenated Diphenyl Ethers) RN - N80BQ29A0H (decabromobiphenyl ether) SB - IM MH - Animals MH - DNA Damage MH - *DNA Methylation MH - Epigenesis, Genetic MH - *Flame Retardants/toxicity MH - Germ Cells MH - Halogenated Diphenyl Ethers/toxicity MH - Male MH - Mice OTO - NOTNLM OT - DNA damage response OT - DNA methylation OT - Decabrominated diphenyl ether (BDE-209) OT - Functional enrichment OT - GC-2spd OT - Germ cell development EDAT- 2021/10/06 06:00 MHDA- 2021/10/07 06:00 CRDT- 2021/10/05 05:40 PHST- 2020/11/02 00:00 [received] PHST- 2021/03/31 00:00 [revised] PHST- 2021/04/01 00:00 [accepted] PHST- 2021/10/05 05:40 [entrez] PHST- 2021/10/06 06:00 [pubmed] PHST- 2021/10/07 06:00 [medline] AID - S1001-0742(21)00134-0 [pii] AID - 10.1016/j.jes.2021.04.001 [doi] PST - ppublish SO - J Environ Sci (China). 2021 Nov;109:161-170. doi: 10.1016/j.jes.2021.04.001. Epub 2021 Apr 24.