title: Folate depletion during pregnancy and lactation reduces genomic DNA methylation in murine adult offspring.
abstract: The developmental origins of adult health and disease (DOHaD) hypothesis that argues for a causal relationship between under-nutrition during early life and increased risk for a range of diseases in adulthood is gaining epidemiological support. One potential mechanism mediating these effects is the modulation of epigenetic markings, specifically DNA methylation. Since folate is an important methyl donor, alterations in supply of this micronutrient may influence the availability of methyl groups for DNA methylation. We hypothesised that low folate supply in utero and post-weaning would alter the DNA methylation profile of offspring. In two separate 2 × 2 factorial designed experiments, female C57Bl6/J mice were fed low- or control/high-folate diets during mating, and through pregnancy and lactation. Offspring were weaned on to either low- or control/high-folate diets, resulting in 4 treatment groups/experiment. Genomic DNA methylation was measured in the small intestine (SI) of 100-day-old offspring. In both experiments, SI genomic DNA from offspring of low-folate-fed dams was significantly hypomethylated compared with the corresponding control/high folate group (P = 0.009/P = 0.006, respectively). Post-weaning folate supply did not affect SI genomic DNA methylation significantly. These observations demonstrate that early life folate depletion affects epigenetic markings, that this effect is not modulated by post-weaning folate supply and that altered epigenetic marks persist into adulthood.
authors.affiliation: Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle, NE2 4HH, UK, jill.mckay@ncl.ac.uk.
authors.forename: Jill A
authors.initials: JA
authors.lastname: McKay
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Waltham
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Williams
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers