Tindula Gwen, Lee Douglas, Huen Karen, Bradman Asa, Eskenazi Brenda, Holland Nina
School of Public Health, Center for Environmental Research and Children's Health, University of California, Berkeley, Berkeley, CA, USA.
Omic Insight, LLC, Durham, NC, USA.
Environ Epigenet. 2019 Apr 1;5(1):dvz004. doi: 10.1093/eep/dvz004. eCollection 2019 Jan.
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.
脂质在许多生物学功能中发挥作用,而新兴的脂质组学领域旨在表征生物样本中存在的各类脂质分子。动物模型已显示孕期母体膳食补充脂肪酸与后代表观遗传变化之间存在关联,这表明产前环境影响儿童结局的一种机制;然而,关于人类孕期母体脂质代谢物水平与新生儿DNA甲基化的数据却很稀少。在本研究中,我们在萨利纳斯母婴健康评估中心队列中评估了孕妇血液中测得的母体脂质代谢物与新生儿DNA甲基化谱之间的关系。通过选择反应监测液相色谱和三重四极杆质谱法进行靶向代谢组学分析,以测量妊娠约26周时孕妇血浆样本中的92种代谢物。使用Infinium HumanMethylation 450K BeadChip评估DNA甲基化,并对脐血细胞组成进行校正。我们发现母体代谢物水平,特别是磷脂和溶血磷脂代谢物与新生儿甲基化之间存在大量经错误发现率校正后的显著关联。观察到的大多数关系为负相关,这表明孕期较高的脂质代谢物与胎儿发育相关基因的较低甲基化水平有关。这些结果进一步阐明了早期生活暴露、母体脂质代谢物和婴儿表观遗传状态之间的复杂关系。