UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers
UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers
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DOI：
10.1039/c2mb05424h
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Gil, Ana M.
中科院分区：
文献类型：
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作者：
Graca, Goncalo;Goodfellow, Brian J.;Gil, Ana M.
我们报告了第一个针对妊娠第二个月母体尿液和羊水 (AF) 的非靶向 UPLC-MS 研究，以研究胎儿畸形 (FM)、妊娠糖尿病 (GDM) 和早产 (PTD) 可能的代谢影响。对于胎儿畸形，在 AF 中发现了相当大的代谢物变异，在尿液中也发现了较小程度的变异。使用经过验证的 PLS-DA 模型以及 UPLC-MS 数据和先前获取的 NMR 数据之间的统计相关性，强化了影响 FM 妊娠的胎儿缺氧、糖异生增强、TCA 活性和肾脏发育受阻的代谢图。此外，最近还注意到肉碱、焦谷氨酸和多元醇的变化，分别反映了脂质氧化、胎盘氨基酸转移的改变和多元醇途径的改变。母体尿液中缀合产物的排泄量较高，表明缀合反应发生了变化。对于诊断前的 GDM 组，无论是羊水还是母体尿液，都没有观察到显着的变化，而对于 PTD 前的组，注意到一些新观察到的变化，即特定氨基酸的减少和己糖（可能是葡萄糖）的增加，表明胎盘氨基酸通量的改变和可能的高血糖趋势。这项工作显示了 UPLC-MS 在研究胎儿和母体生物体液方面的潜力，特别是与可比较的 NMR 数据结合使用时。讨论了采样特征（例如群体维度）所发挥的重要作用以及为 MS 方法选择的具体实验条件。
We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed.