Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA, 98101, USA.
Department of Pediatrics, University of Washington, Seattle, WA, USA.
Curr Environ Health Rep. 2022 Sep;9(3):490-501. doi: 10.1007/s40572-022-00354-8. Epub 2022 Apr 29.
The developmental origins of health and disease (DOHaD) hypothesis posits that the perinatal environment can impact fetal and later life health. The placenta is uniquely situated to assess prenatal exposures in the context of DOHaD because it is an essential ephemeral fetal organ that manages the transport of oxygen, nutrients, waste, and endocrine signals between the mother and fetus. The purpose of this review is to summarize recent studies that evaluated the DOHaD hypothesis in human placentas using epigenomics, including DNA methylation and transcriptomic studies of mRNA, lncRNA, and microRNAs.
Between 2016 and 2021, 28 articles evaluated associations between prenatal exposures and placental epigenomics across broad exposure categories including maternal smoking, psychosocial stressors, chemicals, air pollution, and metals. Sixteen of these studies connected exposures to health outcome such as birth weight, fetal growth, or infant neurobehavior through mediation analysis, identification of shared associations between exposure and outcome, or network analysis. These aspects of infant and childhood health serve as a foundation for future studies that aim to use placental epigenetics to understand relationships between the prenatal environment and perinatal complications (such as preterm birth or fetal growth restriction) or later life childhood health. Placental DNA methylation and RNA expression have been linked to numerous prenatal exposures, such as PM2.5 air pollution, metals, and maternal smoking, as well as infant and childhood health outcomes, including fetal growth and birth weight. Placental epigenomics provides a unique opportunity to expand the DOHaD premise, particularly if research applies novel methodologies such as multi-omics analysis, sequencing of non-coding RNAs, mixtures analysis, and assessment of health outcomes beyond early childhood.
健康与疾病的发育起源（DOHaD）假说认为围产期环境会影响胎儿和生命后期的健康。胎盘在 DOHaD 背景下评估产前暴露的位置独特，因为它是一种重要的短暂胎儿器官，负责在母体和胎儿之间运输氧气、营养物质、废物和内分泌信号。本综述的目的是总结最近使用表观基因组学（包括 DNA 甲基化和 mRNA、lncRNA 和 microRNA 的转录组研究）评估人类胎盘中 DOHaD 假说的研究。
在 2016 年至 2021 年期间，有 28 篇文章评估了广泛的暴露类别（包括母亲吸烟、心理社会压力源、化学物质、空气污染和金属）与胎盘表观基因组学之间的关联。其中 16 项研究通过中介分析、确定暴露与结果之间的共同关联或网络分析，将暴露与出生体重、胎儿生长或婴儿神经行为等健康结果联系起来。这些婴儿和儿童健康方面为未来的研究奠定了基础，这些研究旨在利用胎盘表观遗传学来了解产前环境与围产期并发症（如早产或胎儿生长受限）或生命后期儿童健康之间的关系。胎盘 DNA 甲基化和 RNA 表达已与许多产前暴露（如 PM2.5 空气污染、金属和母亲吸烟）以及婴儿和儿童健康结果（如胎儿生长和出生体重）相关联。胎盘表观基因组学提供了一个独特的机会来扩展 DOHaD 的前提，特别是如果研究采用新的方法，如多组学分析、非编码 RNA 测序、混合物分析以及评估早期儿童以外的健康结果。
