Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm BirthReport as inadecuate




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Background

Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth inflammation, bleeding, the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.

Methodology-Principal Findings

A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight SELDI-TOF mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and-or bleeding proteomic patterns were detected in 32% 92-286 of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity-dissimilarity among proteomic fingerprints. This allowed identification of a novel profile Q-profile based on the presence of 5 SELDI peaks in the 10–12.5 kDa mass area. Women displaying the Q-profile mean±SD, gestational age: 25±4 weeks, n = 40 were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry coupled with Protein ANalysis THrough Evolutionary Relationships PANTHER ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.

Conclusion-Significance

Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity.



Author: Irina A. Buhimschi, Guomao Zhao, Victor A. Rosenberg, Sonya Abdel-Razeq, Stephen Thung, Catalin S. Buhimschi

Source: http://plos.srce.hr/



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