Conclusion
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.
Methods
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.
Results
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).