Unknown,Transcriptomics,Genomics,Proteomics

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The effect of periconceptional micronutrient supplementation on offspring DNA methylation

ABSTRACT: The effect of pre and periconceptional multiple micronutrient supplementation on methylation of CpG loci within CpG islands associated with 14,000 genes across the human genome has been investigated in the offspring of a cohort of Gambian women participating in a controlled double blinded trial. Methylation levels in placebo and micronutrient supplemented cohorts were compared in genomic DNA from cord blood (35 placebo and 21 micronutrient supplemented) and in circulating blood samples (14 placebo and 9 micronutrient supplemented) drawn from the same cohort at 9 months old. A small number of differentially methylated CpG loci were identified in cord blood (14 in males and 21 in females) and a larger number in the 9 month infant comparison (108 in males and 106 in females). Seven differentially methylated loci in males and 8 in females persisted from cord to infant. These findings indicate that micronutrient supplementation pre-conception or early in embryonic development is potentially associated with programming of gene activity at birth, which is maintained into early infanthood. Strikingly, the loci affected by micronutrient supplementation differed between males and females, with no shared changes in cord blood and only 5 shared changes at 9 months. Additionally, a large number of CpG loci showed variation in methylation level when comparing 9-month samples to cord blood samples. These postnatal changes were more consistent between sexes, with 85% of female alterations being found as a subset of male changes in the placebo cohort and 62% of the female changes shared with males in the supplemented cohort. Taken together, the results suggest that there is a core developmental program shared between the sexes that is unaffected by nutrient supplementation, but that there are also sex-specific developmental changes which are altered under conditions of micronutrient supplementation and deficiency. Bisulphite converted DNA from 59 cord (36 placebo and 23 treated) and 25 infant peripheral blood (15 placebo and 10 treated) samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. (For further analysis, five were excluded during quality control leaving 56 cord (35 placebo and 21 treated) and 23 infant peripheral blood (14 placebo and 9 treated) samples. Full data set of 84 samples were submitted to GEO)

ORGANISM(S): Homo sapiens

SUBMITTER: Julien Bauer

PROVIDER: E-GEOD-34257 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.

Khulan Batbayar B Cooper Wendy N WN Skinner Benjamin M BM Bauer Julien J Owens Stephen S Prentice Andrew M AM Belteki Gusztav G Constancia Miguel M Dunger David D Affara Nabeel A NA

Human molecular genetics 20120203 9

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 micron ...[more]

PMID: 22307237

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Project description:A role of vitamin C (ascorbic acid) as an antioxidant molecule has been recognized, largely based on in vitro studies. However, more recently, the concept of M-bM-^@M-^\antioxidant moleculeM-bM-^@M-^] has been reconsidered and its biological function is no longer considered to be simply due to its ability to act as M-bM-^@M-^\electron donorsM-bM-^@M-^], rather, it appears to act by modulating signaling and gene expression. In order to gain a better understanding of the effects of vitamin C supplementation on gene expression in both physiological and pro-inflammatory conditions, we performed a pilot explorative intervention study based on the utilization of microarray and qPCR technologies, designed on a M-bM-^@M-^\in vivo-ex vivoM-bM-^@M-^] structure Five healthy subjects (three males and 2 females, aged 25-40) were recruited for a short term (five days) intervention study. Subjects were asked to assume one tablet of RedoxonM-BM-. (Bayer), a day (containing 1 gr of ascorbate), for 5 days. A baseline blood withdrawal was performed in fasting condition, just before the first vitamin C tablet. Tablets were provided to the volunteers, every morning at the same hour for the following 4 days of the study. The last tablet was supplemented about 1,5 hour before the second and last blood withdrawal, performed again in fasting condition. Plasma and peripheral blood mononuclear cells (PBMNC) were obtained . PBMNC from each subject were splitted in three aliquots: one was stored in lysis buffer at -80M-BM-0C and utilized to isolate RNA for the Affymetrix gene array analysis. The other two aliquots were resuspended in RPMI 1640 w/o phenol red containing 10% of autologous plasma: one was incubated with 10 ug/ml lipopolysaccharides (LPS) for 5 hours at 37M-BM-0C. At the end of the incubation time, the medium was collected and stored at -80M-BM-0C for the assessment of cytokine release in response to the inflammatory stimuli. RNA was extracted from the pelleted cells for gene expression analysis, using the Human NFkB Signaling 96 StellARrayM-bM-^DM-" qPCR array (Lonza). The results obtained with PBMNC isolated after vitamin C supplementation (supplemented PBMNC) were compared to those obtained with PBMNC isolated before the supplementation (baseline PBMNC), for each subject.

Dataset Information

The effect of periconceptional micronutrient supplementation on offspring DNA methylation

Publications

Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.

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