PROTEOMIC PROFILING OF AMNIOS FOR PRETERM BIRTH BIOMARKER DISCOVERY

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. A consistent number of PTB are caused by microbial-induced preterm labor, mediated by an inflammatory process, that threatens both maternal and newborn health. In search for novel predictive biomarkers of PTB and PROM, and to improve understanding of infection related PTB, we performed a proteomic analysis of amnions from premature newborns. Samples were studied by Orbitrap mass spectrometry and bioinformatics analyses. A total of 6352 proteins were identified. A ranked core of 159 proteins maximized the discrimination between the different clinical stratification groups of amnions allowing to distinguish FIR 0 from FIR 3, stratified in function of MIR grade, among which Matrix metallopeptidase 9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential amnion-associated predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.