Metabolomic insights into the lasting impacts of early-life exposure to BDE-47 in mice
Metabolomic insights into the lasting impacts of early-life exposure to BDE-47 in mice
复制标题
从代谢组学角度了解生命早期接触 BDE-47 对小鼠的持久影响
DOI：
10.1016/j.envpol.2020.114524
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发表时间：
2020
影响因子：
8.9
通讯作者：
Si Wei
中科院分区：
文献类型：
--
作者：
Yuqian Li;Nanyang Yu;Meiying Li;Kan Li;Wei Shi;Hongxia Yu;Si Wei
早期接触有毒物质可能会产生持久的影响，对以后的发展产生不利影响。因此，虽然有毒物质的生产和使用已被禁止，但对先前接触过的个人的风险可能会继续存在。BDE-47是商用五溴二苯醚的一个组成部分，是一种持久性有机污染物，已证明具有神经毒性。为了研究BDE-47的持久影响及其机制，我们采用代谢组学方法分析了暴露于BDE-47 28天以及暴露后3个月的小鼠的大脑、血液和尿液。在大脑中，BDE-47在接触后即可检测到，但3个月后低于检测限（LOD）。然而，生命早期接触BDE-47导致的代谢组学改变持续存在。与这些改变相关的潜在生物标志物包括磷脂酰胆碱、溶血磷脂酰胆碱、鞘磷脂和几种氨基酸和生物胺。大脑中对BDE-47产生反应的代谢途径主要涉及甘油磷脂代谢、鞘磷脂代谢和神经递质调节。因此，我们的研究表明，代谢组学作为最能反映表型的组学，在探索生命早期接触BDE-47引起的持久影响的机制方面具有实用性。
Early-life exposure to toxicants may have lasting effects that adversely impact later development. Thus, although the production and use of a toxicant have been banned, the risk to previously exposed individuals may continue. BDE-47, a component of commercial penta-BDEs, is a persistent organic pollutant with demonstrated neurotoxicity. To investigate the persistent effects of BDE-47 and the mechanisms thereof, we employed a metabolomics approach to analyze the brain, blood and urine of mice exposed to BDE-47 for 28 days and then 3 months post-exposure. In the brain, BDE-47 was detectable just after exposure but was below the limit of detection (LOD) 3 months later. However, the metabolomic alterations caused by early-life exposure to BDE-47 persisted. Potential biomarkers related to these alterations included phosphatidylcholine, lysophosphatidylcholine, sphingomyelin and several amino acids and biogenic amines. The metabolic pathways involved in the response to BDE-47 in the brain were mainly those related to glycerophospholipid metabolism, sphingomyelin metabolism and neurotransmitter regulation. Thus, our study demonstrates the utility of metabolomics, as the omics most closely reflecting the phenotype, in exploring the mechanisms underlying the lasting effects induced by early-life BDE-47 exposure.