Effects of dioxin isomers on induction of AhRs and CYP1A1 in early developmental stage embryos of medaka ( Oryzias latipes)

Abstract

The aryl hydrocarbon receptor ( AhR) binds to polyaromatic compounds, including dioxins, and enhances the expression of several target genes, including drug-metabolizing cytochrome P450s ( CYP1As). Four AhR genes ( AhR1b-1, AhR1b-2, AhR2a, and AhR2b) were identified in the medaka genome. The molecular machinery involved in the dioxin response has been clarified chiefly in mammals, although fish models, such as zebrafish ( Danio rerio), medaka ( Oryzias latipes), and Fundulus, are excellent candidates for examining the mechanisms of developmental dioxin toxicity. Using these fish models, several experimental studies investigating the induced expression of CYP1A1 and AhRs, including functional evaluations by 2378T4CDD exposure, have been performed. However, few studies have examined the exposure to other dioxin isomers and it is not certain whether similar induced expressions patterns and toxicity-mediating functions of CYP1A1, AhRs, and AhR repressor ( AhRR) compare with 2378T4CDD exposure. In this study, we investigated the toxicity of 13 dioxin isomers, including 2378T4CDD, and the induced expression of AhRs, AhRR, and CYP1A1 ( CYP1A1_ORYLA) in the early life stages of medaka embryos. After exposure to dioxin isomers for 24–48 h, the expression of AhR2a and CYP1A1_ORYLA correlated to the dioxin toxicity, and AhRR mRNA was widely expressed indicating it modulates AhR activity during the early stages of medaka embryos.