title: Altered placental DNA methylation patterns associated with maternal smoking: current perspectives.
abstract: 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, includingRUNX3,PURA,GTF2H2,GCA,GPR135, andHKR1. The placental methylation status ofRUNX3andNR3C1has 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 theNR3C1,CYP1A1,HTR2A, andHSD11B2genes, 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, includingCYP1A1,CYP19A1,NR3C1, andHTR2A. 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.
authors.affiliation: Penn State Tobacco Center of Regulatory Science, College of Medicine, Department of Public Health Sciences, Hershey, PA, USA.
authors.forename: Jennifer Zj
authors.initials: JZ
authors.lastname: Maccani
authors.affiliation: Penn State Tobacco Center of Regulatory Science, College of Medicine, Department of Public Health Sciences, Hershey, PA, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Maccani
keywords: epigenetics; placenta; pregnancy; prenatal; tobacco