妊娠期孕妇尿液中的外源性雌激素水平及其与代谢相关的改变  

Level of Exoestrogens in Urine of Pregnant Women During Pregnancy and Related Metabolic Changes

作　　者：彭博 杨凯歌 胡康蝶 张舟易 梁红 闫超[1] 吴明媛[1] 王彦[1] Peng Bo;Yang Kaige;Hu Kangdie;Zhang Zhouyi;Liang Hong;Yan Chao;Wu Mingyuan;Wang Yan(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China;Shanghai Institute of Planned Parenthood,Shanghai 200237,China)

机构地区：[1]上海交通大学药学院,上海200240 [2]上海市计划生育研究所,上海200237

出　　处：《生态毒理学报》2023年第2期269-285,共17页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金面上项目(81874307,21874088);上海市科委“科技创新行动计划”(19142203100,2014220400,19DZ2202200)。

摘　　要：外源性雌激素是具有雌激素活性的外源性化学物质,通过模拟或抑制内源性雌激素从而干扰生物体的正常内分泌活动。处于妊娠期的孕妇摄入过量外源性雌激素不仅会对自身产生危害,还会对其胎儿产生不利影响,并且外源性雌激素摄入程度与孕妇代谢过程变化之间具有关联性。本文通过液相色谱-三重四极杆质谱联用技术测定孕妇尿液样本中的8种外源性雌激素含量,并根据样本中的外源性雌激素含量将尿液样本分为外源性雌激素水平不同的3组,在3组间有6种外源性雌激素含量具有显著性差异,其中黄豆苷原、染料木黄酮和肠内酯已被美国环境保护局列入内分泌干扰素审查程序清单中。然后,利用液相色谱-高分辨质谱联用技术分析孕妇尿液样本中的代谢组。通过多维统计分析比较外源性雌激素水平不同的孕妇尿液样本代谢组,同时筛选差异代谢物。根据差异代谢物进行生物信息分析可知,孕妇摄入不同程度外源性雌激素引起的代谢过程变化主要有氨基酸代谢、脂肪酸生物合成、柠檬酸循环和氮代谢过程等。此外,3组样本中表达差异和诊断价值较大的共同差异代谢物有甜菜碱和龙胆酸,它们和体内对抗氧化应激相关。差异代谢物反映了外源性雌激素摄入程度对孕妇代谢过程的影响,可作为生物标志物,并为外源性雌激素作用机制研究提供参考。Exoestrogens are exogenous chemical substances with estrogenic activity,which can affect normal physiological functions by interfering with the endocrine system of humans or other animals.Intake of exoestrogens by pregnant women during pregnancy will not only cause harm to themselves,but also adversely affect their fetuses.Interestingly,there is a possible correlation between the intake level of exoestrogens and changes in the metabolic process of pregnant women.In this paper,first,the content of exoestrogens in urine samples of pregnant women was determined by liquid chromatography-triple quadrupole mass spectrometry,and the samples were classified into three groups,according to the content of exoestrogens,as“high,middle and low”.Among the three groups,the levels of daidzein,genistein,glycitein,enterodiol,enterolactone,and 3-(4-hydroxyphenyl)chroman-7-ol had a significant difference,where three of them,daidzein,genistein and enterolactone,had already been included in the list of Endocrine Disruptor Screening Program by U.S.Environmental Protection Agency.Second,metabolomes of the three groups of urine samples were analyzed by liquid chromatography-high resolution mass spectrometry,then,they were compared by multidimensional statistical analysis,and the differential metabolites were screened.There were 11 up-regulated and 6 down-regulated metabolites screened in the“high”group compared to the“middle”one,and 40 up-regulated and 40 down-regulated metabolites screened in the“middle”one compared to the“low”group.At the same time,comparison of the“high”group vs the“low”one showed 27 up-regulated and 21 down-regulated metabolites.Furthermore,bioinformatics analysis of differential metabolites showed that the metabolic process changes related to the intake level of exoestrogens mainly included amino acid metabolism,fatty acid biosynthesis,citric acid cycle and nitrogen metabolism.In addition,the common differential metabolites with a greater expression difference and diagnostic value were bet

关 键 词：外源性雌激素 孕妇 慢性毒性 氧化损伤 液相色谱-质谱 摄入程度 尿液代谢组学 差异代谢物 

分 类 号：X171.5[环境科学与工程—环境科学]