Impact of In Utero Folate Exposure on DNA Methylation and Its Potential Relevance for Later-Life Health-Evidence from Mouse Models Translated to Human Cohorts.
Impact of In Utero Folate Exposure on DNA Methylation and Its Potential Relevance for Later-Life Health-Evidence from Mouse Models Translated to Human Cohorts.
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DOI：
10.1002/mnfr.202100789
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发表时间：
2022-03
影响因子：
5.2
通讯作者：
McKay JA
中科院分区：
文献类型：
--
作者：
Kok DE;Richmond RC;Adriaens M;Evelo CT;Ford D;Mathers JC;Robinson N;McKay JA
持续的DNA甲基化变化可能介导早期暴露对后期健康的影响。然而，人类寿命对前瞻性研究具有挑战性，因此纵向研究的数据有限。将小鼠早期生活暴露模型的数据投射到现有的人类研究中，为解决这一挑战提供了一个潜在的工具。C57BL/6J小鼠在孕前和哺乳期分别饲喂低叶酸和正常叶酸饲料。在妊娠17.5天和28周的雄性后代肝脏中测量全基因组启动子甲基化。在胎儿和成人中，8个启动子同时因叶酸缺失而高度甲基化（>1.10倍变化；p<0.05）。可能受全球变化影响的过程/途径以及这8个基因的功能提示神经认知效应。人类观察和随机对照试验数据被询问翻译结果。出生时甲基化与母体血浆中6个基因的叶酸含量呈负相关（-1.15%至0.16%/nmol/l, p<0.05），而母体叶酸补充与成年后4个基因的甲基化差异相关。3个CpGs持续高甲基化，母体叶酸水平较低（p=0.04）。在小鼠中观察到的一些持续的叶酸诱导的甲基化变化也反映在人类身上。这证明了小鼠数据在确定人类基因座作为晚年健康的生物标志物方面的效用。
Persistent DNA methylation changes may mediate the effects of early-life exposures on later-life health. However, the human lifespan is challenging for prospective studies, therefore data from longitudinal studies are limited. Projecting data from mouse models of early-life exposure to existing human studies offers a potential tool to address this challenge. C57BL/6J mice were fed low or normal folate diets before and during pregnancy and lactation. Genome-wide promoter methylation was measured in male offspring livers at 17.5 days gestation and 28 weeks. Eight promoters were concurrently hypermethylated by folate depletion in fetuses and adults (>1.10 fold-change;p<0.05). Processes/pathways potentially influenced by global changes, and function of these 8 genes, suggest neurocognitive effects. Human observational and randomized controlled trial data were interrogated for translational findings. Methylation at birth was inversely associated with maternal plasma folate in 6 of the genes (-1.15% to-0.16%/nmol/l;p<0.05), whilst maternal folic acid supplementation was associated with differential methylation of 4 of these genes in adulthood. Three CpGs were persistently hypermethylated with lower maternal folate (p=0.04). Some persistent folate-induced methylation changes observed in mice were mirrored in humans. This demonstrates utility of mouse data in identifying human loci for interrogation as biomarkers of later-life health.
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DOI：
10.1111/1471-0528.13574
发表时间：
2016-02-01
影响因子：
5.8
作者：
Krikke, G. G.;Grooten, I. J.;Painter, R. C.
通讯作者：
Painter, R. C.
影响因子：
3.5
作者：
McKay, Jill A.;Waltham, Kevin J.;Mathers, John C.
通讯作者：
Mathers, John C.
影响因子：
7
作者：
Caffrey, Aoife;McNulty, Helene;Pentieva, Kristina
通讯作者：
Pentieva, Kristina
DOI：
10.1007/978-1-4020-9173-5_13
发表时间：
2009-01-01
期刊：
EARLY NUTRITION PROGRAMMING AND HEALTH OUTCOMES IN LATER LIFE: OBESITY AND BEYOND
影响因子：
--
作者：
Mathers, John C.;Mckay, Jill A.
通讯作者：
Mckay, Jill A.
影响因子：
3.3
作者：
Ansoleaga, B.;Garcia-Esparcia, P.;Ferrer, I.
通讯作者：
Ferrer, I.