Experimental and Behavioral Neurophysiology Lab, Scientific Institute IRCCS Fondazione Santa Lucia, Roma, Italy.
0-3 Center for the At-Risk Infant, Scientific Institute IRCCS E. Medea, Bosisio Parini, Italy.
Neurosci Biobehav Rev. 2021 Jun;125:493-502. doi: 10.1016/j.neubiorev.2021.03.003. Epub 2021 Mar 6.
The first 1000 days from conception are a sensitive period for human development programming. During this period, environmental exposures may result in long-lasting epigenetic imprints that contribute to future developmental trajectories. The present review reports on the effects of adverse and protective environmental conditions occurring during the first 1000 days on glucocorticoid receptor gene (NR3C1) regulation in humans. Thirty-four studies were included. Wide variations emerged for biological tissues, number and position of analyzed CpG sites, and age at methylation and outcomes assessment. Increased NR3C1 methylation associated with first 1000 days stress exposures. Maternal caregiving behaviors significantly buffered precocious stress exposures. A less robust pattern of findings emerged for the association of NR3C1 methylation with physical health, neurobehavioral and neuroendocrine outcomes. Although drawing comprehensive conclusions is partially hindered by methodological limitations, the present review underlines the relevance of the first 1000 days from conception as a time window for developmental plasticity. Prospective cohort studies and epigenome-wide approaches may increase our understanding of dynamics epigenetic changes and their consequences for child development.
受孕后的头 1000 天是人类发育编程的敏感时期。在此期间，环境暴露可能会导致持久的表观遗传印记，从而影响未来的发育轨迹。本综述报告了受孕后头 1000 天内不良和保护的环境条件对人类糖皮质激素受体基因 (NR3C1) 调控的影响。共纳入了 34 项研究。生物组织、分析的 CpG 位点数量和位置，以及甲基化和结果评估的年龄存在很大差异。NR3C1 甲基化与受孕后头 1000 天的应激暴露增加有关。母婴照护行为显著缓冲了过早的应激暴露。NR3C1 甲基化与身体健康、神经行为和神经内分泌结果之间的关联则呈现出一种不那么显著的模式。尽管部分受到方法学限制的影响，难以得出全面的结论，但本综述强调了受孕后头 1000 天作为发育可塑性的时间窗口的重要性。前瞻性队列研究和全基因组表观遗传方法可能会增加我们对动态表观遗传变化及其对儿童发育影响的理解。
