Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation

During preimplantation development, a wave of genome-wide DNA demethylation occurs to acquire a hypomethylated genome of the blastocyst. As an essential epigenomic event, postfertilization DNA demethylation is critical to establish full developmental potential. Despite its importance, this process i...

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Autores principales:	Meiqiang Chu, Fusheng Yao, Guangyin Xi, Jiajun Yang, Zhenni Zhang, Qianying Yang, Jianhui Tian, Lei An
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	vitamin C active DNA demethylation TET dioxygenases preimplantation embryos in vitro fertilization lineage differentiation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6c8f70886f2043cd9f51ea6d8eb3d7d2
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spelling	oai:doaj.org-article:6c8f70886f2043cd9f51ea6d8eb3d7d22021-11-19T07:48:35ZVitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation2296-634X10.3389/fcell.2021.784244https://doaj.org/article/6c8f70886f2043cd9f51ea6d8eb3d7d22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.784244/fullhttps://doaj.org/toc/2296-634XDuring preimplantation development, a wave of genome-wide DNA demethylation occurs to acquire a hypomethylated genome of the blastocyst. As an essential epigenomic event, postfertilization DNA demethylation is critical to establish full developmental potential. Despite its importance, this process is prone to be disrupted due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF), and thus leading to epigenetic errors. However, since the first case of aberrant DNA demethylation reported in IVF embryos, its underlying mechanism remains unclear and the strategy for correcting this error remains unavailable in the past decade. Thus, understanding the mechanism responsible for DNA demethylation defects, may provide a potential approach for preventing or correcting IVF-associated complications. Herein, using mouse and bovine IVF embryos as the model, we reported that ten-eleven translocation (TET)-mediated active DNA demethylation, an important contributor to the postfertilization epigenome reprogramming, was impaired throughout preimplantation development. Focusing on modulation of TET dioxygenases, we found vitamin C and α-ketoglutarate, the well-established important co-factors for stimulating TET enzymatic activity, were synthesized in both embryos and the oviduct during preimplantation development. Accordingly, impaired active DNA demethylation can be corrected by incubation of IVF embryos with vitamin C, and thus improving their lineage differentiation and developmental potential. Together, our data not only provides a promising approach for preventing or correcting IVF-associated epigenetic errors, but also highlights the critical role of small molecules or metabolites from maternal paracrine in finetuning embryonic epigenomic reprogramming during early development.Meiqiang ChuFusheng YaoGuangyin XiJiajun YangZhenni ZhangQianying YangJianhui TianLei AnFrontiers Media S.A.articlevitamin Cactive DNA demethylationTET dioxygenasespreimplantation embryosin vitro fertilizationlineage differentiationBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vitamin C active DNA demethylation TET dioxygenases preimplantation embryos in vitro fertilization lineage differentiation Biology (General) QH301-705.5
spellingShingle	vitamin C active DNA demethylation TET dioxygenases preimplantation embryos in vitro fertilization lineage differentiation Biology (General) QH301-705.5 Meiqiang Chu Fusheng Yao Guangyin Xi Jiajun Yang Zhenni Zhang Qianying Yang Jianhui Tian Lei An Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
description	During preimplantation development, a wave of genome-wide DNA demethylation occurs to acquire a hypomethylated genome of the blastocyst. As an essential epigenomic event, postfertilization DNA demethylation is critical to establish full developmental potential. Despite its importance, this process is prone to be disrupted due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF), and thus leading to epigenetic errors. However, since the first case of aberrant DNA demethylation reported in IVF embryos, its underlying mechanism remains unclear and the strategy for correcting this error remains unavailable in the past decade. Thus, understanding the mechanism responsible for DNA demethylation defects, may provide a potential approach for preventing or correcting IVF-associated complications. Herein, using mouse and bovine IVF embryos as the model, we reported that ten-eleven translocation (TET)-mediated active DNA demethylation, an important contributor to the postfertilization epigenome reprogramming, was impaired throughout preimplantation development. Focusing on modulation of TET dioxygenases, we found vitamin C and α-ketoglutarate, the well-established important co-factors for stimulating TET enzymatic activity, were synthesized in both embryos and the oviduct during preimplantation development. Accordingly, impaired active DNA demethylation can be corrected by incubation of IVF embryos with vitamin C, and thus improving their lineage differentiation and developmental potential. Together, our data not only provides a promising approach for preventing or correcting IVF-associated epigenetic errors, but also highlights the critical role of small molecules or metabolites from maternal paracrine in finetuning embryonic epigenomic reprogramming during early development.
format	article
author	Meiqiang Chu Fusheng Yao Guangyin Xi Jiajun Yang Zhenni Zhang Qianying Yang Jianhui Tian Lei An
author_facet	Meiqiang Chu Fusheng Yao Guangyin Xi Jiajun Yang Zhenni Zhang Qianying Yang Jianhui Tian Lei An
author_sort	Meiqiang Chu
title	Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
title_short	Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
title_full	Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
title_fullStr	Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
title_full_unstemmed	Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation
title_sort	vitamin c rescues in vitro embryonic development by correcting impaired active dna demethylation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6c8f70886f2043cd9f51ea6d8eb3d7d2
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Vitamin C Rescues in vitro Embryonic Development by Correcting Impaired Active DNA Demethylation

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