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产前母体吸烟、DNA 甲基化与组织多组学及其对儿童健康的影响。

Prenatal Maternal Smoke, DNA Methylation, and Multi-omics of Tissues and Child Health.

机构信息

ISGlobal, Institute for Global Health, Barcelona, Spain.

Universitat Pompeu Fabra (UPF), Barcelona, Spain.

出版信息

Curr Environ Health Rep. 2022 Sep;9(3):502-512. doi: 10.1007/s40572-022-00361-9. Epub 2022 Jun 7.

Abstract

PURPOSE OF REVIEW

Maternal tobacco smoking during pregnancy is of public health concern, and understanding the biological mechanisms can help to promote smoking cessation campaigns. This non-systematic review focuses on the effects of maternal smoking during pregnancy on offspring's epigenome, consistent in chemical modifications of the genome that regulate gene expression.

RECENT FINDINGS

Recent meta-analyses of epigenome-wide association studies have shown that maternal smoking during pregnancy is consistently associated with offspring's DNA methylation changes, both in the placenta and blood. These studies indicate that effects on blood DNA methylation can persist for years, and that the longer the duration of the exposure and the higher the dose, the larger the effects. Hence, DNA methylation scores have been developed to estimate past exposure to maternal smoking during pregnancy as biomarkers. There is robust evidence for DNA methylation alterations associated with maternal smoking during pregnancy; however, the role of sex, ethnicity, and genetic background needs further exploration. Moreover, there are no conclusive studies about exposure to low doses or during the preconception period. Similarly, studies on tissues other than the placenta and blood are scarce, and cell-type specificity within tissues needs further investigation. In addition, biological interpretation of DNA methylation findings requires multi-omics data, poorly available in epidemiological settings. Finally, although several mediation analyses link DNA methylation changes with health outcomes, they do not allow causal inference. For this, a combination of data from multiple study designs will be essential in the future to better address this topic.

摘要

综述目的:孕期母体吸烟是公共卫生关注的问题,了解其生物学机制有助于促进戒烟运动。本非系统性综述重点关注孕期母体吸烟对后代表观基因组的影响,即基因组化学修饰对基因表达的调节。

最新发现:最近对全基因组表观遗传关联研究的荟萃分析表明,孕期母体吸烟与后代的 DNA 甲基化变化一致,无论是在胎盘还是血液中。这些研究表明,对血液 DNA 甲基化的影响可以持续多年,并且暴露时间越长、剂量越高,影响就越大。因此,已经开发了 DNA 甲基化评分来估计过去暴露于孕期母体吸烟的情况作为生物标志物。有强有力的证据表明与孕期母体吸烟相关的 DNA 甲基化改变;然而,性别、种族和遗传背景的作用仍需进一步探索。此外,关于低剂量或受孕前暴露的研究尚无定论。同样,除胎盘和血液以外的组织的研究也很少,并且需要进一步研究组织内的细胞特异性。此外,DNA 甲基化发现的生物学解释需要多组学数据,而这些数据在流行病学环境中很难获得。最后,尽管一些中介分析将 DNA 甲基化变化与健康结果联系起来,但它们不能进行因果推断。为此,未来将需要结合多种研究设计的数据,以更好地解决这一问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/996e/9363403/f0ca15b0b602/40572_2022_361_Fig1_HTML.jpg

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