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.

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity

“…PTPRN2 may be a novel, early biomarker for type 2 diabetes [42]. Few studies have previously reported associations of maternal lipids with offspring DNAme, and these were specific analysis of individual genes [19,20,43]. However, the large number of triglyceride-associated DMPs and DMRs near genes involved in lipid metabolism (adipogenesis) in our study supports emerging concepts implicating maternal triglycerides in the epigenetic regulation of growth and development, including excess adiposity.…”

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

“…In previously published work, DNA methylation has been associated with environmental changes in lipid levels. Maternal lipids, passing from mother to child in utero at 26 weeks of gestation, lead to DNA methylation changes in the newborn ( Tindula et al, 2019 ). The lipids associated with DNA methylation changes included phosphatidylcholine and lysolipids – phospholipid degradation products and choline could be an important precursor for DNA methylation.…”

“…Although only a small subset of lipids showed significant associations with GWAM (just 8 individual lipids of 180 non-heritable lipids), these findings do suggest that epigenetic factors such as DNA methylation could explain some In previously published work, DNA methylation has been associated with environmental changes in lipid levels. Maternal lipids, passing from mother to child in utero at 26 weeks of gestation, lead to DNA methylation changes in the newborn58 . The lipids associated with DNA methylation changes included phosphatidylcholine and lysolipidsphospholipid degradation products and choline could be an important precursor for DNA methylation.…”

Dilemma of Epigenetic Changes Causing or Reducing Metabolic Disorders in Offsprings of Obese Mothers

“…Comparison of lipidomic profile between the first-trimester maternal plasma (M1) and delivery maternal plasma (M3) showed that M3 saturated lysophosphatidylcholine is associated with differential methylation at 45 loci and M3 saturated lysophosphatidylethanolamine with 18 differential methylation loci [37]. A negative correlation between the maternal lipid profile including four phospholipids, four lysolipids, and a fatty acid was observed with newborn methylation [38]. A study exemplified that high total cholesterol, low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and triglycerides were linked with 11 significant differential methylated CpGs in the placenta, which play a role in lipid metabolism and were related to dyslipidemia pathways and cardiometabolic disease [39].…”