PUBLICATION
Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
- Authors
- Qian, Y., Wang, C., Wang, J., Zhang, X., Zhou, Z., Zhao, M., Lu, C.
- ID
- ZDB-PUB-170526-22
- Date
- 2017
- Source
- Scientific Reports 7: 2284 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- DNA Methylation/drug effects*
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Embryonic Development/drug effects
- Embryonic Development/genetics
- Gene Expression Regulation, Developmental/drug effects
- Insecticides/chemistry
- Insecticides/toxicity
- Larva/genetics
- Pyrazoles/chemistry
- Pyrazoles/toxicity*
- Stereoisomerism
- Toxicity Tests/methods
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- PubMed
- 28536466 Full text @ Sci. Rep.
- CTD
- 28536466
Citation
Qian, Y., Wang, C., Wang, J., Zhang, X., Zhou, Z., Zhao, M., Lu, C. (2017) Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation. Scientific Reports. 7:2284.
Abstract
Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos. The MeDIP-Seq analysis demonstrated that S-(+)-fipronil dysregulated a higher level of genomic DNA methylation than R-(-)-fipronil. Gene Ontology analysis revealed that S-(+)-fipronil caused more differentially methylated genes that are involved in developmental processes. Compared with R-(-)-fipronil, S-(+)-fipronil significantly disrupted 7 signaling pathways (i.e., mitogen-activated protein kinases, tight junctions, focal adhesion, transforming growth factor-β, vascular smooth muscle contraction, and the hedgehog and Wnt signaling pathways) by hyper-methylation of developmentally related genes, which further induced the downregulation of those genes. Together, these data suggest that differences in DNA methylation may partly explain the enantioselectivity of fipronil to zebrafish embryos. The application of epigenetics to investigate the enantioselective toxicity mechanism of chiral chemicals would provide a further understanding of their stereoselectivity biological effects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping