The legacy pesticide dieldrin acts as a teratogen and alters the expression of dopamine transporter and dopamine receptor 2a in zebrafish (Danio rerio) embryos

Comp Biochem Physiol C Toxicol Pharmacol. 2017 Apr:194:37-47. doi: 10.1016/j.cbpc.2017.01.010. Epub 2017 Feb 3.

Abstract

Dieldrin (DLD) is a lipophilic pesticide that shows environmental persistence. The objectives were to determine the effects of DLD on GABAergic and dopaminergic systems in developing zebrafish. Both chorionated and dechorionated embryos (~24h post-hatch) were exposed to a single concentration of DLD (0.347-3470μM) for 48h. Following exposure, a subset of larvae was placed into clean water for 6days (i.e. depuration phase). Chorionated embryos showed <15% mortality while dechorionated embryos showed higher mortality (>30%), suggesting that the chorion protected the embryos. Over a 6day depuration phase, there was a dose dependent effect observed in both the "dechorionated and chorionated embryo" treatments for larval mortality (>60%). At the end of depuration, there was no detectable change in neuro-morphological endpoints that included the ratio of notochord length to body length (%) and the ratio of head area to body area (%). However, DLD did induce cardiac edema, skeletal deformities, and tremors. GABA-related transcripts were not affected in abundance by DLD. Conversely, the relative mRNA levels of dopamine transporter (dat1) and dopamine receptor drd2a mRNA were decreased in dechorionated, but not chorionated, embryos. These data suggest that DLD can alter the expression of transcripts related to dopaminergic signaling. Lastly, GABAA receptor subunits gabrB1 and gabrB2, as well as dopamine receptors drd1 and drd2a, were inherently higher in abundance in dechorionated embryos compared to chorionated embryos. This is an important consideration when incorporating transcriptomics into embryo testing as expression levels can change with removal of the chorion prior to exposure.

Keywords: Developmental profile; Gamma-amino-butyric acid; Hatch rate; Legacy pesticide; Neurotransmitter; Tyrosine hydroxylase.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Chorion / physiology
  • Dieldrin / toxicity*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / drug effects
  • Gene Expression Regulation, Developmental / drug effects*
  • Insecticides / toxicity*
  • Larva / drug effects
  • Larva / growth & development
  • Larva / metabolism
  • Osmolar Concentration
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Survival Analysis
  • Teratogens / toxicity*
  • Zebrafish / embryology
  • Zebrafish / growth & development
  • Zebrafish / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • GABA-A beta2 receptor, zebrafish
  • Insecticides
  • Protein Isoforms
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, GABA-A
  • SLC6A3 protein, zebrafish
  • Teratogens
  • Zebrafish Proteins
  • Dieldrin