The mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin)-induced toxicity is believed to be mediated by the aryl hydrocarbon receptor (AhR). The role of AhR in embryonic development is not well understood despite evidence suggesting that fetal exposure to dioxin disrupts mammalian preimplantation development, embryonic cell differentiation, reproductive development and sex organ function. We examined zebrafish (Danio rcrio) as a model for studying a role of AhR in development. I)ioxin was acutely toxic to zebrafish embryos. Exposure to 1 nM dioxin for the initial 48 hours post-fertilization resulted in 93% mortality at 5 days post-fertilization compared to 100% survival in the vehicle-exposed group. Temporal expression of AhR was assessed by examining receptor-mediated induction of cytochrome P4501A1 (CYP1A1) by dioxin and 3-methylcholanthrene (3M(l). CYPIAI mRNA was induced in liver, brain and gonads of adult zebrafish exposed to l pM 3MC for 24 hours and in week-old juveniles and embryos exposed to I nM dioxin either 1-24 or 12-36 hours postfertilization. Unfertilized eggs removed from adult female zebrafish exposed to 1 /IM 3MC for 24 hours also expressed CYP1AI mRNA, implying the presence of maternal transcript and a direct effect of in utero exposure to AhR ligands. The presence of AhR-mediated toxicity and enzymatic activity in the embryo suggested that zebrafish are a useful model for studying the developmental rol(, of the AhR.
|Original language||English (US)|
|State||Published - Dec 1 1997|