Pan Jing, Tian Xiujuan, Huang Honglei, Zhong Nanbert
Sanya Maternity and Child Care Hospital, Sanya, China.
Proteomic Core Facility, Oxford University, Oxford, United Kingdom.
Front Physiol. 2020 Jul 21;11:800. doi: 10.3389/fphys.2020.00800. eCollection 2020.
Spontaneous preterm birth (sPTB), which predominantly presents as spontaneous preterm labor (sPTL) or prelabor premature rupture of membranes (PPROM), is a syndrome that accounts for 5-10% of live births annually. The long-term morbidity in surviving preterm infants is significantly higher than that in full-term neonates. The causes of sPTB are complex and not fully understood. Human placenta, the maternal and fetal interface, is an environmental core of fetal intrauterine life, mediates fetal oxygen exchange, nutrient uptake, and waste elimination and functions as an immune-defense organ. In this study, the molecular signature of preterm birth placenta was assessed and compared to full-term placenta by proteomic profiling.
Four groups of fetal membranes (the amniochorionic membranes), with five cases in each group in the discovery study and 30 cases in each group for validation, were included: groups A: sPTL; B: PPROM; C: full-term birth (FTB); and D: full-term premature rupture of membrane (PROM). Fetal membranes were dissected and used for proteome quantification study. Maxquant and Perseus were used for protein quantitation and statistical analysis. Both fetal membranes and placental villi samples were used to validate proteomic discovery.
Proteomics analysis of fetal membranes identified 2,800 proteins across four groups. Sixty-two proteins show statistical differences between the preterm and full-term groups. Among these differentially expressed proteins are (1) proteins involved in inflammation (HPGD), T cell activation (PTPRC), macrophage activation (CAPG, CD14, and CD163), (2) cell adhesion (ICAM and ITGAM), (3) proteolysis (CTSG, ELANE, and MMP9), (4) antioxidant (MPO), (5) extracellular matrix (ECM) proteins (APMAP, COL4A1, LAMA2, LMNB1, LMNB2, FBLN2, and CSRP1) and (6) metabolism of glycolysis (PKM and ADPGK), fatty acid synthesis (ACOX1 and ACSL3), and energy biosynthesis (ATP6AP1 and CYBB).
Our molecular signature study of preterm fetal membranes revealed inflammation as a major event, which is inconsistent with previous findings. Proteolysis may play an important role in fetal membrane rupture. Extracellular matrix s have been altered in preterm fetal membranes due to proteolysis. Metabolism was also altered in preterm fetal membranes. The molecular changes in the fetal membranes provided a significant molecular signature for PPROM in preterm syndrome.
自发性早产（sPTB）主要表现为自发性早产临产（sPTL）或临产前胎膜早破（PPROM），是一种每年占活产儿5 - 10%的综合征。存活的早产儿的长期发病率明显高于足月儿。sPTB的病因复杂，尚未完全明确。人胎盘作为母胎界面，是胎儿宫内生活的环境核心，介导胎儿氧气交换、营养物质摄取和废物排出，并作为免疫防御器官发挥作用。在本研究中，通过蛋白质组学分析评估了早产胎盘的分子特征，并与足月胎盘进行了比较。
纳入四组胎膜（羊膜绒毛膜），发现研究中每组5例，验证时每组30例：A组：sPTL；B组：PPROM；C组：足月产（FTB）；D组：足月胎膜早破（PROM）。解剖胎膜用于蛋白质组定量研究。使用Maxquant和Perseus进行蛋白质定量和统计分析。胎膜和胎盘绒毛样本均用于验证蛋白质组学发现。
对胎膜的蛋白质组学分析在四组中鉴定出2800种蛋白质。62种蛋白质在早产组和足月组之间存在统计学差异。这些差异表达的蛋白质包括：（1）参与炎症的蛋白质（HPGD）、T细胞活化相关蛋白质（PTPRC）、巨噬细胞活化相关蛋白质（CAPG、CD14和CD163）；（2）细胞黏附相关蛋白质（ICAM和ITGAM）；（3）蛋白水解相关蛋白质（CTSG、ELANE和MMP9）；（4）抗氧化相关蛋白质（MPO）；（5）细胞外基质（ECM）蛋白质（APMAP、COL4A1、LAMA2、LMNB1、LMNB2、FBLN2和CSRP1）；（6）糖酵解代谢相关蛋白质（PKM和ADPGK）、脂肪酸合成相关蛋白质（ACOX1和ACSL3）以及能量生物合成相关蛋白质（ATP6AP1和CYBB）。
我们对早产胎膜的分子特征研究表明，炎症是一个主要事件，这与先前的研究结果不一致。蛋白水解可能在胎膜破裂中起重要作用。由于蛋白水解，早产胎膜中的细胞外基质发生了改变。早产胎膜中的代谢也发生了改变。胎膜中的分子变化为早产综合征中的PPROM提供了显著的分子特征。
