Epigenetic Alterations of Maternal Tobacco Smoking during Pregnancy: A Narrative Review

Abstract

In utero exposure to maternal tobacco smoking is the leading cause of birth complications in addition to being associated with later impairment in child’s development. Epigenetic alterations, such as DNA methylation (DNAm), miRNAs expression, and histone modifications, belong to possible underlying mechanisms linking maternal tobacco smoking during pregnancy and adverse birth outcomes and later child’s development. The aims of this review were to provide an update on (1) the main results of epidemiological studies on the impact of in utero exposure to maternal tobacco smoking on epigenetic mechanisms, and (2) the technical issues and methods used in such studies. In contrast with miRNA and histone modifications, DNAm has been the most extensively studied epigenetic mechanism with regard to in utero exposure to maternal tobacco smoking. Most studies relied on cord blood and children’s blood, but placenta is increasingly recognized as a powerful tool, especially for markers of pregnancy exposures. Some recent studies suggest reversibility in DNAm in certain genomic regions as well as memory of smoking exposure in DNAm in other regions, upon smoking cessation before or during pregnancy. Furthermore, reversibility could be more pronounced in miRNA expression compared to DNAm. Increasing evidence based on longitudinal data shows that maternal smoking-associated DNAm changes persist during childhood. In this review, we also discuss some issues related to cell heterogeneity as well as downstream statistical analyses used to relate maternal tobacco smoking during pregnancy and epigenetics. The epigenetic effects of maternal smoking during pregnancy have been among the most widely investigated in the epigenetic epidemiology field. However, there are still huge gaps to fill in, including on the impact on miRNA expression and histone modifications to get a better view of the whole epigenetic machinery. The consistency of maternal tobacco smoking effects across epigenetic marks and across tissues will also provide crucial information for future studies. Advancement in bioinformatic and biostatistics approaches is key to develop a comprehensive analysis of these biological systems.

Higher blood nicotine concentrations following smokeless tobacco (pituri) and cigarette use linked to adverse pregnancy outcomes for central Australian Aboriginal pregnancies

“…Literature from smoked tobacco research indicates a reduction in male newborns in the presence of maternal and/or paternal cigarette smoking in a nicotine dose-dependent manner [103][104][105], and our smokers produced 43% male births, down from the worldwide average of 51.4% [106]. There is emerging evidence that changes to DNA methylation as a result of maternal smoking are greater in male offspring than female offspring [107]. However, while smoking would be expected to be associated with a decrease in birthweight, particularly in male offspring [102], we found male neonates from smokers were 500 g heavier than those from the no-tobacco group while females were on average 280 g lighter.…”

Special Issue on the Effects of Prenatal Smoking/Nicotine Exposure on the Child’s Health

“…The authors provide evidence that maternal smoking associated with DNA methylation changes persist during childhood. Nakamura et al [7] speculate that epigenetic mechanisms could mediate the observed associations between environmental exposures, such as maternal smoking during pregnancy, and later offspring health outcomes but further findings should strengthen this relationship. Furthermore, these effects may transfer beyond the next generation or even beyond.…”

Epigenetic Biomarkers Screening of Non-Coding RNA and DNA Methylation Based on Peripheral Blood Monocytes in Smokers

“…However, the exact mechanism leading to smoking-related diseases and deaths remains largely unknown. Recently, epigenetic regulation has become the focus of research, which can effectively explain many genomic effects that cannot be explained by protein-coding genes ( Nakamura et al, 2021 ; J. L.; Zhang et al, 2019 ).…”