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

机译:CHAMACOS队列的新生儿妊娠脂质组学特征和DNA甲基化

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摘要

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.
机译:脂质在许多生物学功能中发挥作用,脂质组学的新兴领域旨在表征生物样本中存在的不同类别的脂质分子。动物模型显示,孕妇在妊娠期饮食中添加脂肪酸与其后代的表观遗传变化之间存在关联,这说明了产前环境可通过其影响儿童结局的机制。然而,关于怀孕期间孕妇脂质代谢产物水平和人类新生儿DNA甲基化的数据很少。在这项研究中,我们评估了萨利纳斯队列母亲和儿童健康评估中心在孕妇血液中测得的母体脂质代谢产物与新生儿DNA甲基化谱的关系。通过选择的反应监测液相色谱法和三重四极杆质谱法进行靶向代谢组学,以测量妊娠约26周时孕妇血浆样品中的92种代谢物。使用针对脐带血细胞组成进行调节的Infinium HumanMethylation 450K BeadChip评估DNA甲基化。我们发现大量的假发现率与母亲代谢产物水平(尤其是磷脂和溶血脂代谢产物)与新生儿甲基化之间存在显着关联。大多数观察到的关系均为阴性,表明怀孕期间脂质代谢产物较高与与胎儿发育相关的基因甲基化水平较低有关。这些结果进一步阐明了早期生活暴露,母体脂质代谢产物和婴儿表观遗传状态之间的复杂关系。

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