Pregnancy lipidomic profiles and DNA methylation in newborns from the CHAMACOS cohort

Abstract

Lipids play a role in many biological functions and the newly emerging field of lipidomics aims to characterize the varying classes of lipid molecules present in biological specimens. Animal models have shown associations between maternal dietary supplementation with fatty acids during pregnancy and epigenetic changes in their offspring, demonstrating a mechanism through which prenatal environment can affect outcomes in children; however, data on maternal lipid metabolite levels during pregnancy and newborn DNA methylation in humans are sparse. In this study, we assessed the relationship of maternal lipid metabolites measured in the blood from pregnant women with newborn DNA methylation profiles in the Center for the Health Assessment of Mothers and Children of Salinas cohort. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 92 metabolites in plasma samples of pregnant women at ∼26 weeks gestation. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. We uncovered numerous false discovery rate significant associations between maternal metabolite levels, particularly phospholipid and lysolipid metabolites, and newborn methylation. The majority of the observed relationships were negative, suggesting that higher lipid metabolites during pregnancy are associated with lower methylation levels at genes related to fetal development. These results further elucidate the complex relationship between early life exposures, maternal lipid metabolites, and infant epigenetic status.

Keywords: DNA methylation; Mexican-American; cord blood; epigenetics; metabolomics; newborns; prenatal exposure.

Figure 1:

representative histograms of three lipid metabolite classes: (A) a fatty acid, C18:0 FFA; (B) a lysolipid, C18:1 alkyl LPA; and (C) a phospholipid, C18:0e/C18:1 PEe

Figure 2:

median levels of metabolites with ranges in the (A) first (lowest), (B) second, (C) third, and (D) fourth (highest) quartiles. *Represents metabolites that were significantly associated with DNA methylation in newborns

Figure 3:

manhattan plot of CpG sites of CHAMACOS newborns associated with C18:0/C20:4 alkyl PA levels in the blood of their mothers during pregnancy. Red line represents genome-wide significance threshold of −log₁₀(5.00E-08), while the blue line corresponds to the suggestive threshold of −log₁₀(1.00E-05)

Figure 4:

diagram of the significant positive (+) and negative (−) associations observed between maternal metabolites during pregnancy and newborn DNA methylation (A) and the biological pathways whereby maternal lipid levels could impact DNA methylation of their children (B)