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

Bifenthrin is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of bifenthrin increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic pathway components. The dopaminergic neurons can indirectly regulate E2 biosynthesis, suggesting that bifenthrin may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Because embryos do not have a complete HPG axis, the hypothesis that bifenthrin impairs dopamine regulation was tested in embryonic and 1-mo-old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0.34 and 3.1 µg/L bifenthrin for 96 h. Quantitative reverse transcriptase polymerase chain reaction was used to investigate transcripts of tyrosine hydroxylase (TH), dopamine receptor 1 (DR1) and 2A (DR2A), dopamine active transporter (DAT), estrogen receptor α (ERα), ERβ1, ERβ2, luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ), vitellogenin (VTG), cytochrome P450 cyp19a1a, and cyp19a1b. Levels of E2 were measured by enzyme-linked immunosorbent assay (ELISA). Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured by liquid chromatrography-tandem mass spectrometry (LC-MS/MS). Significant decreases in TH and DR1 transcripts and HVA levels, as well as ratios of HVA/dopamine and HVA+DOPAC/dopamine, in zebrafish embryos were observed after bifenthrin treatment. In juveniles, a significant increase in the expression of ERβ1 and the DOPAC to dopamine ratio was noted. These results show a possible antiestrogenic effect of bifenthrin in embryos, and estrogenicity in juveniles, indicating life-stage-dependent toxicity in developing fish. Environ Toxicol Chem 2018;37:236-246.