Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark.
Cell. 2020 Jun 25;181(7):1680-1692.e15. doi: 10.1016/j.cell.2020.05.002.
Metabolism during pregnancy is a dynamic and precisely programmed process, the failure of which can bring devastating consequences to the mother and fetus. To define a high-resolution temporal profile of metabolites during healthy pregnancy, we analyzed the untargeted metabolome of 784 weekly blood samples from 30 pregnant women. Broad changes and a highly choreographed profile were revealed: 4,995 metabolic features (of 9,651 total), 460 annotated compounds (of 687 total), and 34 human metabolic pathways (of 48 total) were significantly changed during pregnancy. Using linear models, we built a metabolic clock with five metabolites that time gestational age in high accordance with ultrasound (R = 0.92). Furthermore, two to three metabolites can identify when labor occurs (time to delivery within two, four, and eight weeks, AUROC ≥ 0.85). Our study represents a weekly characterization of the human pregnancy metabolome, providing a high-resolution landscape for understanding pregnancy with potential clinical utilities.
妊娠期间的代谢是一个动态且精确编程的过程,其失败可能会给母亲和胎儿带来毁灭性的后果。为了定义健康妊娠期间代谢物的高分辨率时间谱,我们分析了 30 名孕妇的 784 个每周血液样本的非靶向代谢组。结果揭示了广泛的变化和高度协调的特征:4995 个代谢特征(9651 个中的),460 个注释化合物(687 个中的)和 34 个人类代谢途径(48 个中的)在妊娠期间发生显著变化。使用线性模型,我们构建了一个具有五个代谢物的代谢钟,其与超声(R = 0.92)高度一致地预测孕龄。此外,两个到三个代谢物可以识别分娩何时发生(分娩时间在两周、四周和八周内,AUROC≥0.85)。我们的研究代表了对人类妊娠代谢组的每周特征描述,为理解妊娠提供了高分辨率的图谱,具有潜在的临床应用价值。