Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.
In addition to the genetic constitution inherited by an organism, the developmental trajectory and resulting mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression. This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life. The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood samples from offspring of Gambian women enrolled into a unique randomized, double blind controlled trial. Significant changes in the epigenome in cord blood DNA samples were further explored in a subset of offspring at 9 months. Gender-specific changes related to periconceptional nutritional supplementation were identified in cord blood DNA samples, some of which showed persistent changes in infant blood DNA samples. Significant effects of periconceptional micronutrient supplementation were also observed in postnatal samples which were not evident in cord blood. In this Gambian population, the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response. Although the sample size was relatively small, these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk.
Mammalian Molecular Genetics Group, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Batbayar
B
Khulan
Wendy N
WN
Cooper
Benjamin M
BM
Skinner
Julien
J
Bauer
Stephen
S
Owens
Andrew M
AM
Prentice
Gusztav
G
Belteki
Miguel
M
Constancia
David
D
Dunger
Nabeel A
NA
Affara
D000293:Adolescent; D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D019587:Dietary Supplements; D004311:Double-Blind Method; D044127:Epigenesis, Genetic; D005260:Female; D005306:Fertilization / Q000235:genetics*; D005312:Fetal Blood / Q000378:metabolism; D005714:Gambia; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000178:diet therapy / Q000235:genetics; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics; D018977:Micronutrients / Q000008:administration & dosage*; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000178:diet therapy / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D011401:Promoter Regions, Genetic; D012727:Sex Characteristics; D055815:Young Adult
D018977:Micronutrients