Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset.
Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset.
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DOI：
10.1126/scitranslmed.abd9898
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发表时间：
2021-05-05
影响因子：
17.1
通讯作者：
Gaudillière B
中科院分区：
文献类型：
--
作者：
Stelzer IA;Ghaemi MS;Han X;Ando K;Hédou JJ;Feyaerts D;Peterson LS;Rumer KK;Tsai ES;Ganio EA;Gaudillière DK;Tsai AS;Choisy B;Gaigne LP;Verdonk F;Jacobsen D;Gavasso S;Traber GM;Ellenberger M;Stanley N;Becker M;Culos A;Fallahzadeh R;Wong RJ;Darmstadt GL;Druzin ML;Winn VD;Gibbs RS;Ling XB;Sylvester K;Carvalho B;Snyder MP;Shaw GM;Stevenson DK;Contrepois K;Angst MS;Aghaeepour N;Gaudillière B
估计分娩时间具有很高的临床重要性，因为产前和产后偏差与母亲及其后代的并发症有关。然而，目前的估计是不准确的。随着妊娠向分娩的进展，母胎免疫、代谢和内分泌系统发生重大转变，最终导致分娩。分娩前母体生物学的全面表征是理解这些生理转变和识别分娩预测生物标志物的关键。在这里，对63名自发分娩的妇女进行了纵向研究。在妊娠最后100天收集的连续血液样本中，使用非靶向质谱法、基于适体的蛋白质组学技术和单细胞质谱仪分析了7000多个血浆分析物和外周免疫细胞反应。将高维数据集整合到预测自然分娩时间的多组学模型中[R = 0.85，95%置信区间（CI）[0.79至0.89]，P = 1.2 × 10 - 40，N = 53，训练集; R = 0.81，95% CI [0.61至0.91]，P = 3.9 × 10−7，N = 10，独立检验集]。母体代谢组、蛋白质组和免疫组的协调改变标志着分娩前2 ~ 4周从妊娠维持到分娩前生物学的分子转变。分娩前类固醇激素代谢产物和白细胞介素-1受体4的激增与从免疫激活到炎症反应调节的转变相吻合。我们的研究为开发基于血液的方法来预测分娩日奠定了基础，这些方法锚定在早产和足月妊娠中共享的机制中。
Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10−40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10−7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
8
作者：
通讯作者：
--
影响因子：
4.3
作者：
Cha, Jeeyeon M.;Aronoff, David M.
通讯作者：
Aronoff, David M.
影响因子：
9.8
作者：
Aghaeepour, Nima;Lehallier, Benoit;Angst, Martin S.
通讯作者：
Angst, Martin S.
影响因子：
3.7
作者：
Finck, Rachel;Simonds, Erin F.;Jager, Astraea;Krishnaswamy, Smita;Sachs, Karen;Fantl, Wendy;Pe'er, Dana;Nolan, Garry P.;Bendall, Sean C.
通讯作者：
Bendall, Sean C.