title: In utero exposures, infant growth, and DNA methylation of repetitive elements and developmentally related genes in human placenta.
abstract: BACKGROUND
  Fetal programming describes the theory linking environmental conditions during embryonic and fetal development with risk of diseases later in life. Environmental insults in utero may lead to changes in epigenetic mechanisms potentially affecting fetal development.
  
  
  OBJECTIVE
  We examined associations between in utero exposures, infant growth, and methylation of repetitive elements and gene-associated DNA in human term placenta tissue samples.
  
  
  METHODS
  Placental tissues and associated demographic and clinical data were obtained from subjects delivering at Women and Infants Hospital in Providence, Rhode Island (USA). Methylation levels of long interspersed nuclear element-1 (LINE-1) and the Alu element AluYb8 were determined in 380 placental samples from term deliveries using bisulfite pyrosequencing. Genomewide DNA methylation profiles were obtained in a subset of 184 samples using the Illumina Infinium HumanMethylation27 BeadArray. Multiple linear regression, model-based clustering methods, and gene set enrichment analysis examined the association between birth weight percentile, demographic variables, and repetitive element methylation and gene-associated CpG locus methylation.
  
  
  RESULTS
  LINE-1 and AluYb8 methylation levels were found to be significantly positively associated with birth weight percentile (p = 0.01 and p < 0.0001, respectively) and were found to differ significantly among infants exposed to tobacco smoke and alcohol. Increased placental AluYb8 methylation was positively associated with average methylation among CpG loci found in polycomb group target genes; developmentally related transcription factor binding sites were overrepresented for differentially methylated loci associated with both elements.
  
  
  CONCLUSIONS
  Our results suggest that repetitive element methylation markers, most notably AluYb8 methylation, may be susceptible to epigenetic alterations resulting from the intrauterine environment and play a critical role in mediating placenta function, and may ultimately inform on the developmental basis of health and disease.
authors: Department of Epidemiology, Center for Environmental Health and Technology, Brown University, Providence, Rhode Island, USA.
authors: Charlotte S
authors: CS
authors: Wilhelm-Benartzi
authors: E Andres
authors: EA
authors: Houseman
authors: Matthew A
authors: MA
authors: Maccani
authors: Graham M
authors: GM
authors: Poage
authors: Devin C
authors: DC
authors: Koestler
authors: Scott M
authors: SM
authors: Langevin
authors: Luc A
authors: LA
authors: Gagne
authors: Carolyn E
authors: CE
authors: Banister
authors: James F
authors: JF
authors: Padbury
authors: Carmen J
authors: CJ
authors: Marsit
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D020087:Alu Elements; D001724:Birth Weight; D002947:Cities / Q000453:epidemiology; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000254:growth & development* / Q000378:metabolism; D007236:Infant, Small for Gestational Age / Q000254:growth & development / Q000378:metabolism; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements; D018811:Maternal Exposure; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000235:genetics; D012237:Rhode Island / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014028:Tobacco Smoke Pollution