Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies have focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. In the present study, the authors used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. The 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 signalling pathways (i.e., mitogen-activated protein kinases, tight junctions, focal adhesion, transforming growth factor-?, vascular smooth muscle contraction, and the hedgehog and Wnt signalling 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.

Authors: Qian Y, Wang C, Wang J, Zhang X, Zhou Z, Zhao M, Lu C. ;Full Source: Science Reports. 2017 May 23;7(1):2284. doi: 10.1038/s41598-017-02255-5. ;