Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum
Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum
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DOI：
10.1016/j.reprotox.2019.05.058
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发表时间：
2019-08-01
影响因子：
3.3
通讯作者：
Cohn, Barbara A.
中科院分区：
文献类型：
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作者：
Hu, Xin;Li, Shuzhao;Cohn, Barbara A.
代谢指纹的高分辨率代谢组学（HRM）分析可以提高对聚和全氟烷基物质（PFAS）如何诱导子宫内环境的代谢改变并影响胎儿健康的理解。对1959-1967年儿童健康与发育研究（CHDS）中收集的397例围产期孕妇血清样本进行了PFAS的HRM分析和定量。我们使用全代谢组关联研究（MWAS）和途径富集分析与全氟辛烷磺酸，其前体EtFOSAA，和EtFOSAA-全氟辛烷磺酸的比例代谢协会。发现EtFOSAA和全氟辛烷磺酸的代谢特征不同。尿素循环代谢物，如精氨酸、赖氨酸和肌酸，与EtFOSAA（阴性）和全氟辛烷磺酸（阳性）呈相反的关系;而肉毒碱穿梭代谢物则与全氟辛烷磺酸完全呈正相关，表明脂肪酸代谢受到干扰。前体和终产物的这些差异代谢关联代表了确定PFAS如何改变子宫内环境并潜在导致疾病风险的重要第一步。
High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk.