Profiling signaling proteins in human spermatozoa: biomarker identification for sperm quality evaluation
Silva JV, Freitas MJ, Correia BR, Korrodi-Gregório L, Patrício A, Pelech S, Fardilha M.
OBJECTIVE: To determine the correlation between semen basic parameters and the expression and activity of signaling proteins. DESIGN: In vitro studies with human spermatozoa. SETTING: Academic research institute. PATIENT(S): Thirty-seven men provided semen samples for routine analysis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): This study contributed toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters. CI - Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Silva, Joana Vieira AU - Silva JV AD - Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal. FAU - Freitas, Maria João AU - Freitas MJ AD - Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal. FAU - Correia, Bárbara Regadas AU - Correia BR AD - Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal. FAU - Korrodi-Gregório, LuÃs AU - Korrodi-Gregório L AD - Laboratory of Signal Transduction, Institute for Research in Biomedicine, Health Sciences Program, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal. FAU - PatrÃcio, António AU - PatrÃcio A AD - Hospital Infante D. Pedro E.P.E., Aveiro, Portugal. FAU - Pelech, Steven AU - Pelech S AD - Kinexus Bioinformatics Corporation, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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