Maternal and neonatal one-carbon metabolites and the epigenome-wide infant response
Carolyn F McCabe1, Jennifer L LaBarre2, Steven E Domino3
1Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
Insights
Maternal one-carbon metabolites, like S-adenosylhomocysteine (SAH), influence infant DNA methylation patterns. Changes in these metabolites during pregnancy are linked to altered DNA methylation in newborns, impacting offspring health.
Area of Science:
- Epigenetics
- Developmental Biology
- Nutritional Biochemistry
Background:
- Maternal prenatal exposures significantly impact offspring health and disease risk.
- DNA methylation (DNAm) alterations are a potential mechanism linking prenatal conditions to later-life disease.
- One-carbon metabolism (OCM) is vital for fetal development and provides methyl donors for DNAm.
Purpose of the Study:
- To investigate the association between maternal one-carbon metabolites during pregnancy and infant cord blood DNA methylation.
- To explore how changes in specific one-carbon metabolites across gestation correlate with epigenetic patterns in newborns.
Main Methods:
- Analysis of plasma one-carbon metabolites (SAH, SAM, betaine, choline) in maternal samples (M1, M3) and infant cord blood (CB).
- Quantification of DNA methylation across the epigenome in infant cord blood using the Illumina Infinium MethylationEPIC BeadChip.
- Statistical modeling adjusted for infant sex, estimated cell type proportions, and batch effects.
Main Results:
- Significant changes in SAH, SAM, betaine, and choline concentrations were observed between the first trimester (M1) and term (M3) of pregnancy.
- Maternal first trimester SAH and cord blood SAH were significantly associated with global DNA methylation patterns in infant cord blood, indicating hypomethylation.
- SAH levels at maternal term (M3) and in cord blood also showed significant associations with locus-specific DNA methylation in infants.
Conclusions:
- Maternal one-carbon metabolites play a crucial role in modulating global DNA methylation patterns in infant cord blood.
- These findings highlight the importance of maternal nutritional status and its influence on the fetal epigenome.
- Further research is needed to understand how dietary factors impact methylation potential and long-term offspring health outcomes.
Abstract:
Maternal prenatal status, as encapsulated by that to which a mother is exposed through diet and environment, is a key determinant of offspring health and disease. Alterations in DNA methylation (DNAm) may be a mechanism through which suboptimal prenatal conditions confer disease risk later in life. One-carbon metabolism (OCM) is critical to both fetal development and in supplying methyl donors needed for DNAm. Plasma concentrations of one-carbon metabolites across maternal first trimester (M1), maternal term (M3), and infant cord blood (CB) at birth were tested for association with DNAm patterns in CB from the Michigan Mother and Infant Pairs (MMIP) pregnancy cohort. The Illumina Infinium MethylationEPIC BeadChip was used to quantitatively evaluate DNAm across the epigenome. Global and single-site DNAm and metabolite models were adjusted for infant sex, estimated cell type proportions, and batch as covariates. Change in mean metabolite concentration across pregnancy (M1 to M3) was significantly different for S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), betaine, and choline. Both M1 SAH and CB SAH were significantly associated with the global distribution of DNAm in CB, with indications of a shift toward less methylation. M3 SAH and CB SAH also displayed significant associations with locus-specific DNAm in infant CB (FDR<0.05). Our findings underscore the role of maternal one-carbon metabolites in shifting the global DNAm pattern in CB and emphasizes the need to closely evaluate how dietary status influences cellular methylation potential and ultimately offspring health.
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