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生命最初 1000 天接触环境空气污染与儿童 DNA 甲基化组和端粒长度的改变:系统评价。

Exposure to ambient air pollution in the first 1000 days of life and alterations in the DNA methylome and telomere length in children: A systematic review.

机构信息

Department of Medical Sciences, University of Turin, CPO Piemonte, Turin, Italy.

Department of Epidemiology, Lazio Regional Health Service, ASL Roma 1, Rome, Italy.

出版信息

Environ Res. 2021 Feb;193:110504. doi: 10.1016/j.envres.2020.110504. Epub 2020 Nov 20.

DOI:10.1016/j.envres.2020.110504
PMID:33221306
Abstract

BACKGROUND

Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children.

METHODS

PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited.

RESULTS

Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure.

CONCLUSIONS

Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.

摘要

背景

生命最初 1000 天(从受孕到 2 岁)期间接触空气污染可能对儿童长期健康特别重要。分子标志物(如 DNA 甲基化和端粒长度)的变化可能是空气污染暴露与污染相关疾病之间关联的基础,也可作为过去暴露的生物标志物。本系统评价的目的是评估妊娠期间和生命最初 2 年期间接触空气污染与儿童 DNA 甲基化或端粒长度变化之间的关系。

方法

2020 年 10 月,使用与环境空气污染暴露、DNA 甲基化、端粒长度和研究人群(母婴对子和儿童)相关的术语在 PubMed 中进行了检索。两名评审员独立完成了筛选和文章选择。符合我们标准的文章有 32 篇。这些文章大多关注妊娠期空气污染暴露,并在新生儿脐带血或胎盘组织中测量 DNA 甲基化/端粒长度,以研究全基因组、候选基因或全基因组甲基化模式和/或端粒长度。关于儿童的研究数量有限。

结果

妊娠期间的环境空气污染暴露与新生儿脐带血和胎盘的全基因组甲基化丢失相关,表明妊娠开始是一个潜在的易感期。候选基因和全基因组关联研究提供了证据,表明妊娠期暴露于空气污染物可导致新生儿脐带血和胎盘中特定基因的甲基化改变,特别是涉及细胞对氧化应激、线粒体功能、炎症、生长和早期发育的基因。在新生儿和儿童中观察到与妊娠期污染物暴露相关的端粒长度缩短。

结论

妊娠期间的环境空气污染与全基因组和特定基因的 DNA 甲基化变化以及端粒长度缩短有关。未来的研究需要在不同人群中检验这种关联的稳健性,探索潜在的易损窗口,并评估甲基化和端粒长度作为早期暴露于环境空气污染物与特定儿童健康结果之间关联的中介作用。

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