PUBLICATION

Exposure of low-dose fipronil enantioselectively induced anxiety-like behavior associated with DNA methylation changes in embryonic and larval zebrafish

Authors
Qian, Y., Ji, C., Yue, S., Zhao, M.
ID
ZDB-PUB-190326-14
Date
2019
Source
Environmental pollution (Barking, Essex : 1987)   249: 362-371 (Journal)
Registered Authors
Keywords
Chiral, DNA methylation, Fipronil, Neurotoxicity
MeSH Terms
  • Animals
  • Anxiety/chemically induced
  • Behavior, Animal/drug effects*
  • DNA Methylation
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/physiology
  • Insecticides/toxicity*
  • Larva/metabolism
  • Pesticides
  • Pyrazoles/toxicity*
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/embryology
  • Zebrafish/metabolism
PubMed
30909129 Full text @ Environ. Pollut.
Abstract
Fipronil, a broad-spectrum chiral insecticide, has been documented to induce significant neurotoxicity to nontarget aquatic species; however, whether its neurotoxicity behaves enantioselectively and what molecular mechanisms correspond to the neurotoxicity remain unanswered. To date, few investigations have focused on the genomic mechanisms responsible for the enantioselective toxicity of chiral pesticides. The epigenetic modifications, especially DNA methylation, caused by the pesticides are also blind spot of the research works. Video tracking showed that R-fipronil exhibited more intense neurotoxicity, as well as the induction of more severe anxiety-like behavior, such as boosted swimming speed and dysregulated photoperiodic locomotion, to embryonic and larval zebrafish compared with S-fipronil. The MeDIP-Seq analysis, combined with Gene Ontology and KEGG, revealed that R-fipronil disrupted five signaling pathways (MAPK, Calcium signaling, Neuroactive ligand-receptor interaction, Purine metabolism, and Endocytosis) to a greater extent than S-fipronil through the hypermethylation of several important neuro-related genes, whereas no significant alterations of global DNA methylation were observed on the two enantiomers. To summarize, our data indicated that the fipronil-conducted enantioselective neurotoxicity likely applied its enantioselectivity by the dysregulation of DNA methylation. Our study also provided novel epigenetic insights into the study of enantioselective biological effects and the relevant underlying mechanisms of chiral insecticide.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping