A temporal high-resolution investigation of the Ah-receptor pathway during early development of zebrafish (Danio rerio)

Aquat Toxicol. 2018 Nov;204:117-129. doi: 10.1016/j.aquatox.2018.09.007. Epub 2018 Sep 15.

Abstract

In order to contribute to a comprehensive understanding of the regulating mechanisms of the aryl-hydrocarbon-receptor (AHR) in zebrafish embryos, we aimed to elucidate the interaction of proteins taking part in this signaling pathway during early development of the zebrafish (Danio rerio) after chemical exposure. We managed to illustrate initial transcription processes of the implemented proteins after exposure to two environmentally relevant chemicals: polychlorinated biphenyl 126 (PCB126) and β-Naphthoflavone (BNF). Using qPCR, we quantified mRNA every 4 h until 118 h post fertilization and found the expression of biotransformation enzymes (cyp1 family) and the repressor of the AHR (ahr-r) to be dependent on the duration of chemical exposure and the biodegradability of the compounds. PCB126 induced persistently increased amounts of transcripts as it is not metabolized, whereas activation by BNF was limited to the initial period of exposure. We did not find a clear relation between the amount of transcripts and activity of the induced CYP-proteins, so posttranscriptional mechanisms are likely to regulate biotransformation of BNF. With regard to zebrafish embryos and their application in risk assessment of hazardous chemicals, our examination of the AHR pathway especially supports the relevance of the time point or period of exposure that is used for bioanalytical investigations and consideration of chemical properties determining biodegradability.

Keywords: Arylhydrocarbon receptor; Biotransformation; Cytochrome P450; Polychlorinated biphenyl 126; Zebrafish embryo; β-Naphthoflavone.

MeSH terms

  • Animals
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development* / drug effects
  • Embryonic Development* / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • Polychlorinated Biphenyls / toxicity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Water Pollutants, Chemical / toxicity
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • beta-Naphthoflavone / toxicity

Substances

  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Water Pollutants, Chemical
  • Zebrafish Proteins
  • beta-Naphthoflavone
  • Polychlorinated Biphenyls