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Perturbed neonatal size is associated with differential DNA methylation and gene expression in human placentas

ABSTRACT: Fetal growth in utero is affected by both inherent genetic programming in combination with environmental factors, such as maternal health and nutrition. Epidemiologic data in growth-altered fetuses, either growth-restricted (IUGR) or large for gestational age (LGA), demonstrate compelling evidence that these fetuses are at increased risk for cardiovascular and metabolic disease in adulthood. In this study, we used RRBS to examine genome wide DNA methylation variation in placental samples from offspring born IUGR, LGA, and appropriate for gestational age (AGA). We identified almost 200 differentially methylated genes among these groups. Among these genes, the differentially methylated regions were disproportionately located in transcription-regulatory regions such as promoters. Our results suggest that the gene expression and methylation state of the human placenta are related and sensitive to the intrauterine environment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70364 | GEO | 2015/06/30

SECONDARY ACCESSION(S): PRJNA288434

REPOSITORIES: GEO

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Project description:INTRODUCTION: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated.MATERIALS AND METHODS: A single center retrospective cohort study was conducted. Newborn infants were enrolled into the study and they were grouped according to their birth weight percentile as small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants. In all infants amino acid and carnitine/acylcarnitine profile with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups.RESULTS: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine and glycine (p<0.05) when compared to AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p<0.05). LGA infants had higher C3 and C5:1 level; and lower C18:2 and C16:1-OH levels (p<0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine and glycine levels (p<0.05). Also a positive correlation between ponderal index and C3, C5-DC, C14, C14:1; and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, C18:2 were shown.CONCLUSION: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

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Perturbed neonatal size is associated with differential DNA methylation and gene expression in human placentas

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