DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell developm

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Decabrominated diphenyl ether(BDE-209)is generally utilized in multiple polymer materi-als 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 devel-opment,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 μg/mL BDE-209 for 24 hr.The results showed that BDE-209 caused genomic methylation changes with 32,083 dif-ferentially 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.
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