A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior

Abstract Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to...

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Autores principales:	Qiao-Qiao Kong, Xiao-Dan Tian, Jia Wang, Hong-Jie Yuan, Shu-Fen Ning, Ming-Jiu Luo, Jing-He Tan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c152e286134d4abd87ee26119efee078
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spelling	oai:doaj.org-article:c152e286134d4abd87ee26119efee0782021-12-02T18:03:07ZA next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior10.1038/s41598-021-87060-x2045-2322https://doaj.org/article/c152e286134d4abd87ee26119efee0782021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87060-xhttps://doaj.org/toc/2045-2322Abstract Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring’s ALB by modifying sperm DNA methylation.Qiao-Qiao KongXiao-Dan TianJia WangHong-Jie YuanShu-Fen NingMing-Jiu LuoJing-He TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qiao-Qiao Kong Xiao-Dan Tian Jia Wang Hong-Jie Yuan Shu-Fen Ning Ming-Jiu Luo Jing-He Tan A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
description	Abstract Pathophysiological mechanisms for depression/anxiety are largely unknown. Evidence for transgenerational transmission of acquired epigenetic marks remains limited. We bred unstressed (US) female mice with adolescently restraint-stressed (RS), social instability-stressed (SI) or US males to produce RS, SI and control F1 offspring, respectively. Compared to controls, while paternal RS decreased anxiety-like behavior (ALB) in both female and male offspring, paternal SI increased ALB only in female offspring. Next-generation sequencing and bioinformatics using RS and SI female offspring identified 5 candidate anxiety-transmitting (CAT) genes; each showed a consistent pattern of DNA methylation from F0 spermatozoa through F1 blastocysts to fetal and adult hippocampi. Further analyses validated 4 CAT genes, demonstrated that paternal SI caused ALB differences between male and female offspring through modifying the CAT genes, and indicated a strong correlation between inflammation and ALB pathogenesis and an important function for intronic DNA methylation in regulating ALB-related genes. In conclusion, this study identified important CAT genes and suggested the possibility that stresses on males might alter offspring’s ALB by modifying sperm DNA methylation.
format	article
author	Qiao-Qiao Kong Xiao-Dan Tian Jia Wang Hong-Jie Yuan Shu-Fen Ning Ming-Jiu Luo Jing-He Tan
author_facet	Qiao-Qiao Kong Xiao-Dan Tian Jia Wang Hong-Jie Yuan Shu-Fen Ning Ming-Jiu Luo Jing-He Tan
author_sort	Qiao-Qiao Kong
title	A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
title_short	A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
title_full	A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
title_fullStr	A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
title_full_unstemmed	A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
title_sort	next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c152e286134d4abd87ee26119efee078
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A next-generation sequencing study on mechanisms by which restraint and social instability stresses of male mice alter offspring anxiety-like behavior

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