Early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate induces delayed neurotoxicity associated with DNA methylation in adult zebrafish

Early-life exposure to toxicants could affect health outcomes in adulthood. We determined the effects of early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in adult zebrafish. Embryos were exposed to TDCIPP from early embryogenesis (2 h post-fertilization) to 10 days post-fertilization (dpf), and larvae were transferred to clean water until adulthood (150 dpf). TDCIPP showed accumulation in larvae, but returned to control levels after 7 days of depuration. In adult zebrafish exposed to TDCIPP in early life, vulnerability to anxiety-like behavior was observed in females but not males, suggesting gender-dependent neurotoxicity. Decreased dopamine (DA) concentration and down-regulation of dopaminergic signaling related genes were observed in the brains of adult females. Upregulation of DNA methylation transferases (dnmt1, dnmt3a, and dnmt3b) genes were observed in larvae and brains of adult females. Further, the promoter regions of the selected key genes (bdnf, drd4b, zc4h2 and th) showed increased DNA methylation status, accompanied by down-regulation of gene transcription in larvae and brains of adult females. Our results indicate that early-life exposure to TDCIPP could cause delayed neurotoxicity in adult zebrafish. Keywords: Tris (1,3-dichloro-2-propyl) phosphate, Delayed neurotoxicity, Dopaminergic neurons, DNA methylation, Zebrafish