An initial proteomic analysis of human preterm labor: placental membranes.
Human preterm labor (PL) is the single most significant problem in modern Obstetrics and Gynecology, affecting approximately 10% of pregnancies worldwide, constituting the leading cause of perinatal mortality and morbidity, and contributing significantly to chronic childhood disease. Currently, our molecular understanding of PL remains staggeringly inadequate to reliably diagnose or rationally intervene in PL events; several molecular alterations have been implicated in PL, but these have proven of limited value as diagnostic/prognostic markers. The majority of PL events remain spontaneous and unpredictable: critical care emergencies. Here, we apply functional proteomics to dissect molecular mechanisms of human PL. Human placental tissue was collected in clearly differentiated cases of preterm and term labor. Highly refined two-dimensional gel electrophoresis (2DE) was used for protein separation, coupled with automated differential gel image analysis to compare the resulting proteomic maps. For this initial study, only the most important protein differences were selected for further analysis, that is, proteins that were unique to one sample, and absent from the other, with 100% reproducibility across the sample population. In total, 11 such proteins were identified by tandem mass spectrometry, falling into three distinct functional classes: structural/cytoskeletal components, ER lumenal proteins with enzymatic or chaperone functions, and proteins with anticoagulant properties. These expression changes form the groundwork for further molecular investigation of this devastating medical condition. This approach therefore holds the potential not only to define the underlying molecular components, but also to identify novel diagnostic tools and targets for rational drug intervention.
Butt
R Hussain
RH
Department of Physiology & Biophysics, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Lee
Maggie W Y
MW
Pirshahid
S Ahmadi
SA
Backlund
Peter S
PS
Wood
Stephen
S
Coorssen
Jens R
JR
D000925:Anticoagulants / Q000302:isolation & purification; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification; D008970:Molecular Weight; D007752:Obstetric Labor, Premature / Q000378:metabolism*; D010920:Placenta / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000302:isolation & purification; D040901:Proteomics / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results
D000925:Anticoagulants; D008565:Membrane Proteins; D011257:Pregnancy Proteins