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孕期运动的孕妇所生后代中胰岛素样生长因子2的甲基化差异

Differential methylation of insulin-like growth factor 2 in offspring of physically active pregnant women.

作者信息

Marshall M R, Paneth N, Gerlach J A, Mudd L M, Biery L, Ferguson D P, Pivarnik J M

机构信息

1Department of Kinesiology,Samford University,Birmingham,AL,USA.

2Department of Epidemiology & Biostatistics,Michigan State University,East Lansing,MI,USA.

出版信息

J Dev Orig Health Dis. 2018 Jun;9(3):299-306. doi: 10.1017/S2040174417001106. Epub 2018 Jan 9.

Abstract

Several studies have suggested that maternal lifestyle during pregnancy may influence long-term health of offspring by altering the offspring epigenome. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have this effect is unknown. The purpose of this study was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation. Participants were recruited from the Archive for Research on Child Health study. At enrollment, participants' demographic information and self-reported LTPA during pregnancy were determined. High active participants (averaged 637.5 min per week of LTPA; n=14) were matched by age and race to low active participants (averaged 59.5 min per week LTPA; n=28). Blood spots were obtained at birth. Pyrosequencing was used to determine methylation levels of long interspersed nucleotide elements (LINE-1) (global methylation) and peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), insulin-like growth factor 2 (IGF2), pyruvate dehydrogenase kinase, isozyme 4 (PDK4) and transcription factor 7-like 2 (TCF7L2). We found no differences between offspring of high active and low active groups for LINE-1 methylation. The only differences in candidate gene methylation between groups were at two CpG sites in the P2 promoter of IGF2; the offspring of low active group had significantly higher DNA methylation (74.70±2.25% methylation for low active v. 72.83±2.85% methylation for high active; P=0.045). Our results suggest no effect of maternal LTPA on offspring global and candidate gene methylation, with the exception of IGF2. IGF2 has been previously associated with regulation of physical activity, suggesting a possible role of maternal LTPA on regulation of offspring physical activity.

摘要

多项研究表明,孕期母亲的生活方式可能通过改变子代表观基因组来影响子代的长期健康。孕期母亲的休闲体育活动(LTPA)是否会产生这种影响尚不清楚。本研究的目的是确定孕期母亲LTPA与子代DNA甲基化之间的关系。参与者来自儿童健康研究档案。在入组时,确定参与者的人口统计学信息以及其孕期自我报告的LTPA情况。高活动量参与者(平均每周LTPA为637.5分钟;n = 14)按年龄和种族与低活动量参与者(平均每周LTPA为59.5分钟;n = 28)进行匹配。在出生时采集血斑。焦磷酸测序用于确定长散在核苷酸元件(LINE-1)(整体甲基化)以及过氧化物酶体增殖物激活受体γ(PPARγ)、过氧化物酶体增殖物激活受体γ共激活因子(PGC1-α)、胰岛素样生长因子2(IGF2)、丙酮酸脱氢酶激酶同工酶4(PDK4)和转录因子7样2(TCF7L2)的甲基化水平。我们发现,高活动量组和低活动量组子代的LINE-1甲基化没有差异。两组候选基因甲基化的唯一差异在于IGF2的P2启动子中的两个CpG位点;低活动量组子代的DNA甲基化显著更高(低活动量组甲基化为74.70±2.25%,高活动量组为72.83±2.85%甲基化;P = 0.045)。我们的结果表明,除IGF2外,孕期母亲LTPA对子代整体和候选基因甲基化没有影响。IGF2此前已与身体活动的调节相关联,提示孕期母亲LTPA在调节子代身体活动方面可能发挥作用。

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