The developmental origins of health and disease hypothesis states that adverse
early life exposures can have lasting, detrimental effects on lifelong health. Exposure to
maternal cigarette smoking during pregnancy is associated with morbidity and mortality in
offspring, including increased risks for miscarriage, stillbirth, low birth weight,
preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal
cigarette smoking during pregnancy interferes with placental growth and functioning, and
it has been proposed that this may occur through the disruption of normal and necessary
placental epigenetic patterns. Epigenome-wide association studies have identified a number
of differentially methylated placental genes that are associated with maternal smoking
during pregnancy, including RUNX3, PURA,
GTF2H2, GCA, GPR135, and
HKR1. The placental methylation status of RUNX3 and
NR3C1 has also been linked to adverse infant outcomes, including
preterm birth and low birth weight, respectively. Candidate gene analyses have also found
maternal smoking-associated placental methylation differences in the
NR3C1, CYP1A1, HTR2A, and
HSD11B2 genes, as well as in the repetitive elements LINE-1 and AluYb8.
The differential methylation patterns of several genes have been confirmed to also exhibit
altered gene expression patterns, including CYP1A1,
CYP19A1, NR3C1, and HTR2A. Placental
methylation patterns associated with maternal smoking during pregnancy may be largely
gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is
important for future research to investigate the mechanistic roles that these
differentially methylated genes may play in mediating the association between maternal
smoking during pregnancy and disease in later life, as well as to elucidate the potential
influence of emerging tobacco product use during pregnancy, including the use of
electronic cigarettes, on placental epigenetics.