Department of Obstetrics and Gynecology, Shaoxing Maternity and Child Health Care Hospital, Shaoxing 312000, Zhejiang Province, China.
School of Medicine, Shaoxing University, Shaoxing 312000, Zhejiang Province, China.
Mol Omics. 2023 Jun 12;19(5):418-428. doi: 10.1039/d2mo00305h.
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatobiliary disease, leading to an abnormal increase in total bile acid in the blood of pregnant women. To systematically explore the similarities and differences in metabolites and metabolic pathways among three types of biological samples from ICP women, a study of 18 ICP and 6 healthy (as a normal control) pregnant women was performed to investigate their clinical information and biochemical features. Based on validated LC-MS/MS methods 1-5 for hydrophilic and hydrophobic metabolites (molecular weight <2000 Dalton), an untargeted-metabolomic strategy was applied to 24 pregnant women to determine the metabolites from 22 serum, 15 placental and 22 urine samples. Then 1137 metabolites from serum, 876 metabolites from placental tissue and 311 metabolites from urine with a coefficient of variation <30% in the pooled quality control samples were found. Furthermore, orthogonal partial least squares-discriminate analysis (OPLS-DA), correlation analysis, chemical enrichment analysis and metabolic pathway analysis were carried out by a bioinformatics process. On the OPLS-DA model analysis, the metabolites in urine were better than those in serum or placental tissue to reflect the metabolic changes of ICP disease. Some metabolites were significantly changed in serum ( = 71), placental tissue ( = 46) and urine ( = 36), such as bile acids, triacylglycerols, lysoPCs, and steroids. Primary bile acid biosynthesis was the main metabolic pathway in ICP disease, and taurine and hypotaurine metabolism and sphingolipid metabolism were also found. More specifically, bile acids increased and steroids decreased in the serum, placental and urine samples. For complex metabolic diseases such as ICP disease, untargeted-metabolomic analysis of multiple biological samples could provide a systematic understanding of the changes in metabolic types and pathways.
妊娠肝内胆汁淤积症（ICP）是一种妊娠特有的肝胆疾病，导致孕妇血液中总胆汁酸异常升高。为了系统地探讨 ICP 妇女三种生物样本中代谢物和代谢途径的异同，对 18 例 ICP 和 6 例健康（作为正常对照）孕妇进行了研究，以研究其临床信息和生化特征。基于已验证的用于亲水和疏水代谢物（分子量<2000 道尔顿）的 LC-MS/MS 方法 1-5，应用非靶向代谢组学策略对 24 例孕妇进行了研究，以确定来自 22 例血清、15 例胎盘和 22 例尿液样本的代谢物。然后，在混合质量控制样本中，发现了 1137 种血清代谢物、876 种胎盘组织代谢物和 311 种尿液代谢物，其变异系数<30%。此外，通过生物信息学过程进行了正交偏最小二乘判别分析（OPLS-DA）、相关性分析、化学富集分析和代谢途径分析。在 OPLS-DA 模型分析中，尿液中的代谢物比血清或胎盘组织中的代谢物更能反映 ICP 疾病的代谢变化。一些代谢物在血清（=71）、胎盘组织（=46）和尿液（=36）中发生显著变化，如胆汁酸、三酰甘油、溶血磷脂酰胆碱和类固醇。ICP 疾病的主要代谢途径是初级胆汁酸生物合成，还发现了牛磺酸和次牛磺酸代谢和鞘脂代谢。更具体地说，在血清、胎盘和尿液样本中，胆汁酸增加，类固醇减少。对于 ICP 等复杂代谢性疾病，对多种生物样本进行非靶向代谢组学分析可以提供对代谢类型和途径变化的系统理解。
