MP70-15 PROFILING SIGNALING PROTEINS IN HUMAN SPERMATOZOA: BIOMARKER IDENTIFICATION FOR SPERM QUALITY EVALUATION

Abstract

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology1 Apr 2016MP70-15 PROFILING SIGNALING PROTEINS IN HUMAN SPERMATOZOA: BIOMARKER IDENTIFICATION FOR SPERM QUALITY EVALUATION ANTONIO PATRICIO, JOANA SILVA, NUNO MAIA, SAUL ALMEIDA, JOAO LOURENÇO, MARGARIDA FARDILHA, and STEVEN PELECH ANTONIO PATRICIOANTONIO PATRICIO More articles by this author , JOANA SILVAJOANA SILVA More articles by this author , NUNO MAIANUNO MAIA More articles by this author , SAUL ALMEIDASAUL ALMEIDA More articles by this author , JOAO LOURENÇOJOAO LOURENÇO More articles by this author , MARGARIDA FARDILHAMARGARIDA FARDILHA More articles by this author , and STEVEN PELECHSTEVEN PELECH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sperm cells are incapable of genetic expression and thus highly dependent upon post-translational modifications and signal cascades to execute their function. However, not much information is available on the biological significance of specific signaling pathways in human spermatozoa or their possible roles in male infertility. In this study we attempted to unravel the signaling pathways involved in regulating human sperm function and to correlate the activity of signaling proteins with clinical data. METHODS We included 37 human semen samples, obtained from a randomized group of donors. Basic semen parameters were analyzed according to the WHO’s guidelines. Sperm DNA fragmentation (SDF) was measured using a Sperm Chromatin Dispersion (SCD) test. Antibody-based arrays were carried out to determine the expression patterns of 18 well-characterized signaling molecules when phosphorylated or cleaved. A commercial Kinetworks™ Protein Kinase Screen was used to analyze the levels of 75 protein kinases. RESULTS Phosphorylated levels of several proteins [Bad, GSK-3ß, 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. 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 TZI, as well as, the presence of head defects. In contrast, SDF negatively correlated with morphologically normal spermatozoa and the phosphorylation of Akt and p70 S6 kinase. Subjects with varicocele showed a negative correlation between head morphological defects and the phosphorylated levels of Akt, GSK3ß, p38 MAPK and Stat1. Additionally, 34 protein kinases were identified as expressed in their total protein levels in normozoospermic samples. From those, 8 protein kinases were identified for the first time human spermatozoa. CONCLUSIONS This study contributed towards establishing a biomarker “fingerprint” to assess sperm quality based on molecular parameters. Proteins with a high degree of differential activity have the potential to integrate a quantitative array to: (1) overcome the subjectivity of the spermogram; (2) explain idiopathic infertility, failure in ART or repeated abortion; (3) choice of the appropriate ART; and (4) assess the efficacy of medical interventions. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e912 Advertisement Copyright & Permissions© 2016MetricsAuthor Information ANTONIO PATRICIO More articles by this author JOANA SILVA More articles by this author NUNO MAIA More articles by this author SAUL ALMEIDA More articles by this author JOAO LOURENÇO More articles by this author MARGARIDA FARDILHA More articles by this author STEVEN PELECH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...