title: Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy.
abstract: The intrauterine environment has the potential to "program" the developing fetus in a way that can be potentially deleterious to later health. While in utero environmental/stochastic factors are known to influence DNA methylation profile at birth, it has been difficult to assign specific examples of epigenetic variation to specific environmental exposures. Recently, several studies have linked exposure to smoking with DNA methylation change in the aryl hydrocarbon receptor repressor (AHRR) gene in blood. This includes hypomethylation of AHRR in neonatal blood in response to maternal smoking in pregnancy. The role of AHRR as a negative regulator of pathways involved in pleiotropic responses to environmental contaminants raises the possibility that smoking-induced hypomethylation is an adaptive response to an adverse in utero environmental exposure. However, the tissue specificity of the response to maternal smoking, and the stability of the methylation changes early in life remain to be determined. In this study we analyzed AHRR methylation in three cell types-cord blood mononuclear cells (CBMCs), buccal epithelium, and placenta tissue-from newborn twins of mothers who smoked throughout pregnancy and matched controls. Further, we explored the postnatal stability of this change at 18 months. Our results confirm the previous association between maternal smoking and AHRR methylation in neonatal blood. In addition, this study expands the region of AHRR methylation altered in response to maternal smoking during pregnancy and reveals the tissue-specific nature of epigenetic responses to environmental exposures in utero. Further, the evidence for postnatal stability of smoking-induced epigenetic change supports a role for epigenetics as a mediator of long-term effects of specific in utero exposures in humans. Longitudinal analysis of further specific exposures in larger cohorts is required to examine the extent of this phenomenon in humans.
authors.affiliation: Cancer, Disease and Developmental Epigenetics; Murdoch Childrens Research Institute; Royal Children's Hospital; Parkville, VIC Australia.
authors.forename: Boris
authors.initials: B
authors.lastname: Novakovic
authors.affiliation: Cancer, Disease and Developmental Epigenetics; Murdoch Childrens Research Institute; Royal Children's Hospital; Parkville, VIC Australia; Department of Paediatrics; University of Melbourne; Parkville, VIC Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
authors.affiliation: Metabolomics Australia; School of Botany; The University of Melbourne; Parkville, VIC Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Pereira
authors.affiliation: Metabolomics Australia; School of Botany; The University of Melbourne; Parkville, VIC Australia.
authors.forename: Berin
authors.initials: B
authors.lastname: Boughton
authors.affiliation: Department of Paediatrics; University of Melbourne; Parkville, VIC Australia; Early Life Epigenetics; Murdoch Childrens Research Institute; Royal Children's Hospital; Parkville, VIC Australia; Department of Paediatrics; University of Melbourne; Parkville, VIC Australia.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Craig
authors.affiliation: Cancer, Disease and Developmental Epigenetics; Murdoch Childrens Research Institute; Royal Children's Hospital; Parkville, VIC Australia; Department of Paediatrics; University of Melbourne; Parkville, VIC Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D009928:Organ Specificity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; C492162:AHRR protein, human
keywords: Aryl hydrocarbon receptor repressor (AHRR); Cord blood mononuclear cells; DNA methylation; DOHaD; early life epigenetics; intrauterine environment; smoking; twins