Division of Maternal-Fetal Medicine & Perinatal Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas.
Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, Louisiana.
Endocrinology. 2018 May 1;159(5):2229-2240. doi: 10.1210/en.2018-00073.
Our objective was to determine the amniotic fluid-derived exosomal proteomic profile in patients who had spontaneous preterm birth (PTB) or preterm premature rupture of membranes (pPROM) compared with those who delivered at term. A cross-sectional study of a retrospective cohort was used to quantify and determine the protein content of exosomes present in amniotic fluid, in PTB or pPROM, and normal term labor (TL) or term not in labor (TNIL) pregnancies. Exosomes were isolated by differential centrifugation and quantified using nanocrystals (Qdot) coupled to CD63 and placental alkaline phosphatase (PLAP) by fluorescence nanoparticle tracking analysis. The exosomal proteomic profile was identified by liquid chromatography-tandem mass spectrometry, and a small ion library was constructed to quantify the proteomic data by Sequential Window Acquisition of All Theoretical analysis. Ingenuity Pathway Analysis determined canonical pathways and biofunctions associated with dysregulated proteins. Amniotic fluid exosomes have similar shape and quantity regardless of the conditions; however, the PLAP/CD63 ratios for TL, PTB, and pPROM were significantly higher (∼3.8-, ∼4.4-, and ∼3.5-fold, respectively) compared with TNIL. The PLAP/CD63 ratio was also significantly higher (∼1.3-fold) in PTB compared with pPROM. Biological functions primarily indicated nonspecific inflammatory response regardless of condition, but unique profiles were also identified in cases (PTB and pPROM) compared with term. Amniotic fluid exosomes provide information specific to normal and abnormal parturition. Inflammatory marker enrichment and its uniqueness in term and preterm pregnancies support the value of exosomes in determining underlying physiology associated with term and preterm parturition.
我们的目的是确定与足月分娩（TL）或足月未临产（TNIL）妊娠相比，自发性早产（PTB）或早产胎膜早破（pPROM）患者的羊水来源外泌体蛋白质组谱。使用回顾性队列的横断面研究来定量和确定存在于羊水、PTB 或 pPROM 中的外泌体的蛋白质含量，以及正常 TL 或 TNIL 妊娠。通过差速离心分离外泌体，并通过荧光纳米颗粒跟踪分析用与 CD63 和胎盘碱性磷酸酶（PLAP）偶联的纳米晶体（Qdot）定量。通过液相色谱-串联质谱鉴定外泌体蛋白质组谱，并通过 Sequential Window Acquisition of All Theoretical 分析构建小离子文库来定量蛋白质组数据。通路分析确定了与失调蛋白相关的经典途径和生物功能。无论条件如何，羊水外泌体的形状和数量都相似；然而，TL、PTB 和 pPROM 的 PLAP/CD63 比值显著更高（分别约为 3.8、4.4 和 3.5 倍），与 TNIL 相比。PTB 中的 PLAP/CD63 比值也显著高于 pPROM（约 1.3 倍）。无论条件如何，生物学功能主要表明非特异性炎症反应，但也在病例（PTB 和 pPROM）中鉴定出独特的谱。羊水外泌体提供与正常和异常分娩相关的特定信息。炎症标志物的富集及其在足月和早产妊娠中的独特性支持外泌体在确定与足月和早产分娩相关的潜在生理学方面的价值。
