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Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth

Authors :
Stephen F. Thung
Sonya S. Abdel-Razeq
Victor A. Rosenberg
Guomao Zhao
Irina A. Buhimschi
Catalin S. Buhimschi
Source :
PLoS ONE, PLoS ONE, Vol 3, Iss 4, p e2049 (2008)
Publication Year :
2008
Publisher :
Public Library of Science, 2008.

Abstract

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.

Details

Language :
English
ISSN :
19326203
Volume :
3
Issue :
4
Database :
OpenAIRE
Journal :
PLoS ONE
Accession number :
edsair.doi.dedup.....ae9db5ce0b385c1fdc37551c046b0635