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

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 meth...

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Autores principales:	Yi Qian, Cui Wang, Jinghua Wang, Xiaofeng Zhang, Zhiqiang Zhou, Meirong Zhao, Chensheng Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/56abacd262a146cdba430546a6cb6db1
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spelling	oai:doaj.org-article:56abacd262a146cdba430546a6cb6db12021-12-02T11:41:12ZFipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation10.1038/s41598-017-02255-52045-2322https://doaj.org/article/56abacd262a146cdba430546a6cb6db12017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02255-5https://doaj.org/toc/2045-2322Abstract 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.Yi QianCui WangJinghua WangXiaofeng ZhangZhiqiang ZhouMeirong ZhaoChensheng LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Qian Cui Wang Jinghua Wang Xiaofeng Zhang Zhiqiang Zhou Meirong Zhao Chensheng Lu Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
description	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.
format	article
author	Yi Qian Cui Wang Jinghua Wang Xiaofeng Zhang Zhiqiang Zhou Meirong Zhao Chensheng Lu
author_facet	Yi Qian Cui Wang Jinghua Wang Xiaofeng Zhang Zhiqiang Zhou Meirong Zhao Chensheng Lu
author_sort	Yi Qian
title	Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
title_short	Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
title_full	Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
title_fullStr	Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
title_full_unstemmed	Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation
title_sort	fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in dna methylation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/56abacd262a146cdba430546a6cb6db1
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Fipronil-induced enantioselective developmental toxicity to zebrafish embryo-larvae involves changes in DNA methylation

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