title: Profiling signaling proteins in human spermatozoa: biomarker identification for sperm quality evaluation.
abstract: OBJECTIVE
  To determine the correlation between semen basic parameters and the expression and activity of signaling proteins.
  
  
  METHODS
  In vitro studies with human spermatozoa.
  
  
  METHODS
  Academic research institute.
  
  
  METHODS
  Thirty-seven men provided semen samples for routine analysis.
  
  
  METHODS
  None.
  
  
  METHODS
  Basic semen parameters tracked included sperm DNA fragmentation (SDF), the expression levels of 75 protein kinases, and the phosphorylation/cleavage patterns of 18 signaling proteins in human spermatozoa.
  
  
  RESULTS
  The results indicated that the phosphorylated levels of several proteins (Bad, GSK-3β, HSP27, JNK/SAPK, mTOR, p38 MAPK, and p53), as well as cleavage of PARP (at D214) and Caspase-3 (at D175), were significantly correlated with motility parameters. Additionally, the percentage of morphologically normal spermatozoa demonstrated a significant positive correlation with the phosphorylated levels of p70 S6 kinase and, in turn, head defects and the teratozoospermia index (TZI) showed a significant negative correlation with the phosphorylated levels of Stat3. There was a significant positive correlation between SDF and the teratozoospermia index, as well as the presence of head defects. In contrast, SDF negatively correlated with the percentage of morphologically normal spermatozoa and the phosphorylation of Akt and p70 S6 kinase. Subjects with varicocele demonstrated a significant negative correlation between head morphological defects and the phosphorylated levels of Akt, GSK3β, p38 MAPK, and Stat1. Additionally, 34 protein kinases were identified as expressed in their total protein levels in normozoospermic samples.
  
  
  CONCLUSIONS
  This study contributed toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters.
authors.affiliation: Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Joana Vieira
authors.initials: JV
authors.lastname: Silva
authors.affiliation: Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Freitas
authors.affiliation: Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Bárbara Regadas
authors.initials: BR
authors.lastname: Correia
authors.affiliation: Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Korrodi-Gregório
authors.affiliation: Hospital Infante D. Pedro E.P.E., Aveiro, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Patrício
authors.affiliation: Kinexus Bioinformatics Corporation, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Pelech
authors.affiliation: Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal. Electronic address: mfardilha@ua.pt.
authors.forename: Margarida
authors.initials: M
authors.lastname: Fardilha
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D053938:DNA Fragmentation; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D055101:Semen Analysis / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010750:Phosphoproteins
keywords: Human spermatozoa; conventional semen parameters; molecular markers; signaling pathways