title: Maternal folate supply and sex influence gene-specific DNA methylation in the fetal gut.
abstract: METHODS
  Epidemiological evidence supports the developmental origins of health and disease hypothesis that developmental under/over-nutrition increases adulthood disease risk. Epigenetic markings are one potential mechanism mediating these effects. Altered folate supply may influence methyl group availability for DNA methylation. We reported low folate supply in utero was associated with reduced global DNA methylation in the murine small intestine of adult offspring. We hypothesised that aberrant methylation would be observed during early development.
  
  
  RESULTS
  Female C57BL/6J mice were fed diets containing 2 mg folic acid/kg or 0.4 mg folic acid/kg 4 wk before mating and during pregnancy. At 17.5 day gestation, gene methylation in fetal gut was analysed by Pyrosequencing(®) . Low folate reduced overall methylation of Slc394a by 3.4% (p=0.038) but did not affect Esr1 or Igf2 differentially methylated region (DMR) 1. There were sex-specific differences in Slc394a and Esr1 methylation (2.4% higher in females (p=0.002); 4% higher in males (p=0.0014), respectively).
  
  
  CONCLUSIONS
  This is the first study reporting causal effects of maternal folate depletion on gene-specific methylation in fetal gut. These observations support reports that altered methyl donor intake during development affects DNA methylation in the offspring. The consequences of epigenetic changes for health throughout the life course remain to be investigated.
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. jill.mckay@ncl.ac.uk
authors.forename: Jill A
authors.initials: JA
authors.lastname: McKay
authors.forename: Yi K
authors.initials: YK
authors.lastname: Wong
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.forename: Dianne
authors.initials: D
authors.lastname: Ford
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D047109:Fetal Development; D048070:Fetal Nutrition Disorders / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000196:embryology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000196:embryology* / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011897:Random Allocation; D012727:Sex Characteristics
chemical_list: D027682:Cation Transport Proteins; D047628:Estrogen Receptor alpha; C513121:IGF2 protein, mouse; C477530:Slc39a4 protein, mouse; D007335:Insulin-Like Growth Factor II; D005492:Folic Acid