Metabolomics Identifies a Panel of Diagnostic Biomarkers for Early Human Embryonic Development Arrest

Early embryonic development arrest (EEDA) is a unique form of early spontaneous abortion in pregnant women, which is previously suggested to be associated with metabolic abnormalities. Noninvasive biomarkers would significantly improve its diagnosis and clinical outcome. Here, we performed a targeted metabolomics study in plasma from EEDA patients (n = 27) and normal pregnant women (NPW, n = 27) using liquid chromatography coupled with mass spectrometry (LC–MS) to identify potential diagnostic marker metabolites. Our results showed significantly different plasma metabolic profiles between EEDA patients and NPW. Particularly, EEDA patients showed significant alterations in amino acid, carbohydrate, and vitamin metabolism, which were characterized by 21 significantly increased metabolites and five decreased metabolites in plasma. Further receiver operating characteristic analysis showed that an optimal combination of S-methyl-5′-thioadenosine, kynurenine, leucine, and malate could be used as a panel of metabolites for EEDA diagnosis. The area under the curve of the metabolite panel was 0.941, suggesting a better performance than any single metabolite for the diagnosis of EEDA. In summary, our study identifies a panel of differential metabolites in plasma that could act as potential biomarkers for the diagnosis of EEDA in clinical settings.早期胚胎发育停滞（Early embryonic development arrest, EEDA）是孕妇早期自发性流产的一类特殊亚型，既往研究表明其与代谢异常密切相关。无创生物标志物可显著提升其诊断效能并优化临床结局。本研究采用液相色谱-质谱联用法（Liquid Chromatography Coupled with Mass Spectrometry, LC–MS），对27例EEDA患者与27例正常妊娠妇女（Normal Pregnant Women, NPW）的血浆样本开展靶向代谢组学研究，以筛选潜在的诊断性代谢标志物。研究结果显示，EEDA患者与正常妊娠妇女的血浆代谢谱存在显著差异。具体而言，EEDA患者的氨基酸、碳水化合物及维生素代谢通路发生显著紊乱，表现为血浆中21种代谢物水平显著上调，5种代谢物水平显著下调。进一步的受试者工作特征（Receiver Operating Characteristic, ROC）曲线分析显示，S-甲基-5'-硫代腺苷、犬尿氨酸、亮氨酸与苹果酸的最优组合可作为EEDA诊断的代谢标志物组。该标志物组的曲线下面积达0.941，表明其诊断性能优于任一单一代谢物。综上，本研究鉴定出一组血浆差异代谢物，可作为临床环境中诊断EEDA的潜在生物标志物。