Effects of bifenthrin exposure on the estrogenic and dopaminergic pathways in zebrafish embryos and juveniles

Bifenthrin (BF) is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of BF increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic (DA) pathway components. DA neurons can indirectly regulate E2 biosynthesis, suggesting that BF may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Since embryos do not have a complete HPG axis, the hypothesis that BF impairs DA regulation was tested in embryonic and one-month old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0.34 and 3.1 µg/L BF for 96 hours. Transcripts of tyrosine hydroxylase (TH), dopamine receptor 1 (DR1) and 2A (DR2A), dopamine active transporter (DAT), estrogen receptor α (ERα), ERβ1, ERβ2, LHβ, FSHβ, vitellogenin (VTG), cytochrome P450 cyp19a1a and cyp19a1b were investigated by qRT-PCR. Levels of E2 were measured by ELISA. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured by LC-MS/MS. Significant decreases of TH and DR1 transcripts, and HVA levels as well as ratios of HVA/DA and HVA + DOPAC/DA in zebrafish embryos were observed after BF treatment. In juveniles, a significant increase in the expression of ERβ1 and the DOPAC/DA ratio was noted. These results show a possible anti-estrogenic effect of BF in embryos, and estrogenicity in juveniles, indicating life-stage dependent toxicity in developing fish. This article is protected by copyright. All rights reserved