孕期前后的娱乐性身体活动与胎盘 DNA 甲基化：一项全基因组关联研究。
Recreational physical activity before and during pregnancy and placental DNA methylation-an epigenome-wide association study.
机构信息
Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Am J Clin Nutr. 2022 Oct 6;116(4):1168-1183. doi: 10.1093/ajcn/nqac111.
BACKGROUND
Physical activity (PA) prior to and during pregnancy may have intergenerational effects on offspring health through placental epigenetic modifications. We are unaware of epidemiologic studies on longitudinal PA and placental DNA methylation.
OBJECTIVES
We evaluated the association between PA before and during pregnancy and placental DNA methylation.
METHODS
Placental tissues were obtained at delivery and methylation was measured using HumanMethylation450 Beadchips for participants in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons among 298 participants. Using the Pregnancy Physical Activity Questionnaire, women recalled periconception PA (past 12 mo) at 8-13 wk of gestation and PA since last visit at 4 follow-up visits at 16-22, 24-29, 30-33, and 34-37 wk. We conducted linear regression for associations of PA at each visit with methylation controlling for false discovery rate (FDR). Top 100 CpGs were queried for enrichment of functional pathways using Ingenuity Pathway Analysis.
RESULTS
Periconception PA was significantly associated with 1 CpG site. PA since last visit for visits 1-4 was associated with 2, 2, 8, and 0 CpGs (log fold changes ranging from -0.0319 to 0.0080, after controlling for FDR). The largest change in methylation occurred at a site in TIMP2 , which is known to encode a protein critical for vasodilation, placentation, and uterine expansion during pregnancy (log fold change: -0.05; 95% CI: -0.06, -0.03 per metabolic equivalent of task-h/wk at 30-33 wk). Most significantly enriched pathways include cardiac hypertrophy signaling, B-cell receptor signaling, and netrin signaling. Significant CpGs and enriched pathways varied by visit.
CONCLUSIONS
Recreational PA in the year prior and during pregnancy was associated with placental DNA methylation. The associated CpG sites varied based on timing of PA. If replicated, the findings may inform the mechanisms underlying the impacts of PA on placenta health. This study was registered at clinicaltrials.gov as NCT00912132.
背景
在妊娠前和妊娠期间进行身体活动（PA）可能会通过胎盘表观遗传修饰对后代健康产生代际影响。我们不知道关于纵向 PA 和胎盘 DNA 甲基化的流行病学研究。
目的
我们评估了妊娠前和妊娠期间 PA 与胎盘 DNA 甲基化之间的关系。
方法
在 298 名参与者中，来自 Eunice Kennedy Shriver 国立儿童健康与人类发育研究所胎儿生长研究- singleton 研究的参与者在分娩时获得胎盘组织，并使用 HumanMethylation450 Beadchips 测量甲基化。使用妊娠体力活动问卷，女性在妊娠 8-13 周时回忆过去 12 个月的围孕期 PA，在 4 次随访时回忆上次就诊后至妊娠 16-22、24-29、30-33 和 34-37 周的 PA。我们进行了线性回归，以关联每次就诊时的 PA 与甲基化，控制假发现率（FDR）。使用 Ingenuity 通路分析查询前 100 个 CpG 以富集功能途径。
结果
围孕期 PA 与 1 个 CpG 位点显著相关。自上次就诊以来的 PA 在就诊 1-4 次时与 2、2、8 和 0 个 CpG 相关（在控制 FDR 后，log 倍数变化范围为-0.0319 至 0.0080）。最大的甲基化变化发生在 TIMP2 中的一个位点，该位点已知编码一种在怀孕期间对血管舒张、胎盘形成和子宫扩张至关重要的蛋白质（log 倍数变化：-0.05；95%CI：-0.06，-0.03 每代谢当量任务小时/周在 30-33 周）。最显著富集的途径包括心肌肥厚信号、B 细胞受体信号和轴突导向信号。显著的 CpG 位点和富集途径因就诊次数而异。
结论
妊娠前一年和妊娠期间的休闲性 PA 与胎盘 DNA 甲基化有关。相关的 CpG 位点随 PA 的时间而变化。如果得到复制，这些发现可能为 PA 对胎盘健康影响的机制提供信息。本研究在 clinicaltrials.gov 上注册为 NCT00912132。
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