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  • Title: Enhancement of sperm-zona pellucida (ZP) binding capacity by activation of protein kinase A and C pathways in certain infertile men with defective sperm-ZP binding.
    Author: Liu DY, Liu ML, Baker HW.
    Journal: Hum Reprod; 2009 Jan; 24(1):20-7. PubMed ID: 18784086.
    Abstract:
    BACKGROUND: Defective sperm-zona pellucida (ZP) binding (DSZPB) is a common cause of failure of fertilization in vitro. This study was to determine if DSZPB is caused by defective pathways upstream of protein kinase A (PKA) and C (PKC), or reduced protein tyrosine phosphorylation (TP). METHODS: Infertile men with DSZPB and either normal sperm morphology (NSM) > or = 14% (n = 15) or < or =5% (n = 15) were studied. Sperm-ZP binding test was performed by incubation of motile sperm with oocytes for 2 h with or without dibutyryl cyclic AMP (dbcAMP, PKA activator) or phorbol myristate acetate (PMA, PKC activator). TP of capacitated sperm in medium was assessed by immunofluorescence with an anti-phosphotyrosine monoclonal antibody. RESULTS: For normal sperm with normal sperm-ZP binding, both PMA and dbcAMP significantly enhanced sperm-ZP binding in a dose-response manner. Only dbcAMP, but not PMA, significantly increased TP of capacitated sperm. In DSZPB men with severe teratozoospermia (NSM < or = 5%), neither PMA nor dbcAMP enhanced sperm-ZP binding, despite dbcAMP significantly increasing the TP of capacitated sperm for all samples. In contrast, for DSZPB with NSM > or = 14%, PMA caused significantly increased sperm binding up to normal levels (> or =40 sperm bound/ZP) in five men, and dbcAMP had a similar result in two men. Again TP was significantly enhanced only by dbcAMP, but not by PMA. CONCLUSIONS: There is defective signalling in pathways upstream of PKC and PKA in some men with DSZPB and normal semen analysis. Stimulation of TP by dbcAMP does not enhance sperm-ZP binding capacity in DSZPB men with low TP, regardless of sperm morphology.
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