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

Environ Toxicol Chem. 2018 Jan;37(1):236-246. doi: 10.1002/etc.3951. Epub 2017 Nov 2.

Abstract

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. © 2017 SETAC.

Keywords: Developmental toxicity; Dopaminergic pathway; Endocrine-disrupting compounds; Estrogenic pathway; Pyrethroids; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Dopamine / metabolism*
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism*
  • Environmental Exposure / analysis*
  • Estrogens / metabolism*
  • Gene Expression Regulation, Developmental / drug effects
  • Homovanillic Acid / metabolism
  • Metabolome
  • Organ Specificity
  • Pyrethrins / toxicity*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Water Pollutants, Chemical / toxicity
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Estrogens
  • Pyrethrins
  • RNA, Messenger
  • Water Pollutants, Chemical
  • Zebrafish Proteins
  • 3,4-Dihydroxyphenylacetic Acid
  • bifenthrin
  • Dopamine
  • Homovanillic Acid