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Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group UK, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Insecticides
Embryo, Nonmammalian
Science
Developmental toxicity
Embryonic Development
Biology
Article
03 medical and health sciences
chemistry.chemical_compound
Toxicity Tests
Animals
Epigenetics
Zebrafish
Fipronil
Regulation of gene expression
Multidisciplinary
Gene Expression Regulation, Developmental
Stereoisomerism
Methylation
DNA Methylation
Zebrafish Proteins
Molecular biology
Cell biology
030104 developmental biology
chemistry
Larva
DNA methylation
Toxicity
Pyrazoles
Medicine
Vascular smooth muscle contraction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....467d7997f7b6d646308d22cae38c67d1
- Full Text :
- https://doi.org/10.1038/s41598-017-02255-5