Division of Maternal-Fetal Medicine & Perinatal Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
Translational Health Science and Technology Institute of India, Faridabad, Haryana, India.
Endocrinology. 2020 Apr 1;161(4). doi: 10.1210/endocr/bqaa009.
Spontaneous preterm birth (PTB) is a major obstetrical problem around the globe and the mechanisms leading to PTB are unclear. Recently, changes in the circulating levels of placental extracellular vesicles (EVs) during pregnancy have been associated with various pregnancy complications. However, progress in the field is hindered by the inability to isolate placental EVs from the maternal circulation. A longitudinal study design was used to determine the protein cargo present in circulating placental EVs in maternal plasma of term and PTB across gestation (ie, first, second, and third trimester). Placental-derived EVs were enriched from the total EV population based on their expression of membrane-bound placental alkaline phosphatase (PLAP). A quantitative, information-independent acquisition (sequential windowed acquisition of all theoretical mass spectra [SWATH]) approach identified and quantified the placental EV protein contents. PLAP+ EVs did not change in characteristics (size, shape, and markers) but did differ in numbers across gestation with low levels in PTB. A comparison analysis between the PLAP+ EV proteome from term and PTB revealed 96 proteins differing significantly (P < 0.05, false discovery rate 1%) across gestation. Bioinformatics analysis of differentially expressed proteins revealed consistent upregulation of inflammatory pathways in both upregulation of epithelial mesenchymal transition pathways at term and downregulation of coagulation/complement activation in preterm. Characterization of the proteomic profile in PLAP+ EVs across gestation demonstrates dramatic changes, which might be used to understand the biological process associated with early parturition and develop biomarkers for predicting high-risk status for PTB.
自发性早产 (PTB) 是全球范围内的一个主要产科问题，导致 PTB 的机制尚不清楚。最近，怀孕期间循环中胎盘细胞外囊泡 (EV) 的水平变化与各种妊娠并发症有关。然而，该领域的进展受到无法将胎盘 EV 从母体循环中分离出来的阻碍。采用纵向研究设计，确定了妊娠期间（即第一、第二和第三 trimester）足月和 PTB 产妇血浆中循环胎盘 EV 中存在的蛋白质货物。基于膜结合胎盘碱性磷酸酶 (PLAP) 的表达，从总 EV 群体中富集胎盘来源的 EV。定量、信息独立获取（所有理论质谱的顺序窗口采集 [SWATH]）方法鉴定和定量了胎盘 EV 蛋白含量。PLAP+ EV 在特征（大小、形状和标记物）上没有变化，但在整个妊娠期的数量上有所不同，PTB 时数量较低。对足月和 PTB 的 PLAP+ EV 蛋白质组进行比较分析，发现 96 种蛋白质在整个妊娠期差异显著（P < 0.05，假发现率 1%）。差异表达蛋白质的生物信息学分析显示，在足月时，炎症途径的一致上调，上皮间质转化途径的上调，以及早产时凝血/补体激活的下调。PLAP+ EV 中跨妊娠的蛋白质组学特征表明发生了剧烈变化，这可能有助于了解与早期分娩相关的生物学过程，并开发预测 PTB 高危状态的生物标志物。
