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

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. Summary 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.

A novel approach to risk exposure and epigenetics—the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health

“…We used this constellation of risks to reveal how early experiences influence the root of health during foetal development, branching into tissues and organs as phenotypic offshoots after birth, as hypothesised in DOHaD theory [ 56 – 58 ]. This may account for how NCDs associated with prenatal smoke exposure have a wide breadth of effects, such as respiratory, cardiometabolic, cognitive, and psychological morbidities [ 10 , 11 , 13 , 15 ]. Pleiotropy is when a single gene contributes to more than one unrelated phenotypic trait, and it occurs frequently in NCDs [ 59 , 60 ].…”

“…A disease-based bias currently exists, as the vast majority of gene annotations originate from repositories collected for cancers, rare diseases, or diseases mainly relevant to populations of European ancestry [ 82 ]. These potential biases are barriers to addressing the bench-to-bedside gap [ 5 , 10 , 78 ] as well as social disparities [ 83 ] in NCD research. As well, we are unaware of any epigenetic studies that have used a multidimensional, population-based measure of risk related to smoking to model foetal programming.…”

“…lower socioeconomic status [ 9 ]). It also has known direct effects on the foetal environment and physiology [ 10 ]. Lastly, it is a common foetal exposure linked to a broad range of NCDs in later life [ 11 – 16 ].…”

Polymorphisms in Glutathione S-Transferase (GST) Genes Modify the Effect of Exposure to Maternal Smoking Metabolites in Pregnancy and Offspring DNA Methylation

“…This may imply that maternal nicotine metabolites may serve as surrogates for tobacco smoke chemicals that affect offspring DNAm through different biological mechanisms in addition to increasing oxidative stress. One of these CpGs is cg05575921 (in the body of the AHRR gene), whose lower methylation has been reported consistently as a marker of exposure to MSP [ 55 , 56 ]. Although significantly associated with nicotine metabolites, DNAm at cg05575921 was not influenced by GST SNPs in our study.…”

Prenatal Environmental Stressors and DNA Methylation Levels in Placenta and Peripheral Tissues of Mothers and Neonates Evaluated by Applying Artificial Neural Networks

“…In this way, the placenta is crucial in mediating the effect of the environment on the child health development programming, as it orchestrates the development and regulation of the foetal environment [ 9 ]. Indeed, several studies conducted in humans and rodents have linked various prenatal factors, including maternal psychosocial stress, maternal smoking and exposure to air pollutants, metals and chemicals, to the placental DNA methylation and gene expression levels, as well as to infant and childhood health outcomes [ 10 , 11 , 12 , 13 ]. From these studies, a plethora of critical genes involved in different cellular pathways, such as growth, metabolism or neuronal plasticity, have been identified as epigenetically modulated.…”