DNA methylation alterations in response to prenatal exposure of maternal cigarette smoking: A persistent epigenetic impact on health from maternal lifestyle?

Arch Toxicol. 2016 Feb;90(2):231-45. doi: 10.1007/s00204-014-1426-0. Epub 2014 Dec 6.


Despite increased awareness, maternal cigarette smoking during pregnancy continues to be a common habit causing risk for numerous documented negative health consequences in the exposed children. It has been proposed that epigenetic mechanisms constitute the link between prenatal exposure to maternal cigarette smoking (PEMCS) and the diverse pathologies arising in later life. We here review the current literature, focusing on DNA methylation. Alterations in the global DNA methylation patterns were observed after exposure to maternal smoking during pregnancy in placenta, cord blood and buccal epithelium tissue. Further, a number of specific genes exemplified by CYP1A1, AhRR, FOXP3, TSLP, IGF2, AXL, PTPRO, C11orf52, FRMD4A and BDNF are shown to have altered DNA methylation patterns in at least one of these tissue types due to PEMCS. Investigations showing persistence and indications of trans-generational inheritance of DNA methylation alterations induced by smoking exposure are also described. Further, smoking-induced epigenetic manifestations can be both tissue-dependent and gender-specific which show the importance of addressing the relevant sex, tissue and cell types in the future studies linking specific epigenetic alterations to disease development. Moreover, the effect of paternal cigarette smoking and second-hand smoke exposure is documented and accordingly not to be neglected in future investigations and data evaluations. We also outline possible directions for the future research to address how DNA methylation alterations induced by maternal lifestyle, exemplified by smoking, have direct consequences for fetal development and later in life health and behavior of the child.

Keywords: DNA methylation; Developmental origins of health and disease (DOHaD); Environment; Epigenetics; Smoking; Trans-generational effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Methylation / drug effects*
  • Epigenesis, Genetic / drug effects*
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Maternal Exposure
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Smoking / adverse effects*