Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth.
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.


RESULTS
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.


CONCLUSIONS
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.
Buhimschi
Irina A
IA
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, United States of America. irina.buhimschi@yale.edu
Zhao
Guomao
G
Rosenberg
Victor A
VA
Abdel-Razeq
Sonya
S
Thung
Stephen
S
Buhimschi
Catalin S
CS
D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006470:Hemorrhage; D006801:Humans; D007249:Inflammation; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D047928:Premature Birth / Q000209:etiology*; D020543:Proteome / Q000032:analysis / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012984:Software; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016896:Treatment Outcome; D014470:Umbilical Cord / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; D011257:Pregnancy Proteins; D020543:Proteome; D012333:RNA, Messenger