craig-postnatalstability-2014.pdf (1.85 MB)
Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy
journal contribution
posted on 2014-03-01, 00:00 authored by Boris Novakovic, Joanne Ryan, Natalie Pereira, Berin Boughton, Jeffrey CraigJeffrey Craig, Richard SafferyThe 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.
History
Journal
EpigeneticsVolume
9Issue
3Pagination
377 - 386Publisher
Taylor & FrancisLocation
London, Eng.Publisher DOI
ISSN
1559-2294eISSN
1559-2308Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2014, Landes BioscienceUsage metrics
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Keywords
Fetal BloodHumansPrenatal Exposure Delayed EffectsRepressor ProteinsCase-Control StudiesSmokingMaternal ExposureOrgan SpecificityDNA MethylationEpigenesis, GeneticPregnancyMaternal-Fetal ExchangeInfant, NewbornFemaleBasic Helix-Loop-Helix Transcription FactorsScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyGenetics & HeredityDOHaDAryl hydrocarbon receptor repressor (AHRR)Cord blood mononuclear cellstwinsintrauterine environmentearly life epigeneticsARYL-HYDROCARBON RECEPTOREPIGENOME-WIDE ASSOCIATIONEPIGENETIC EPIDEMIOLOGYDEVELOPMENTAL ORIGINSMASS-SPECTROMETRYGENETIC-FACTORSHUMAN PLACENTAADULT DISEASEGenetics
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