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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) ≥ 14% (n = 15) 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 ≤ 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 ≥ 14%, PMA caused significantly increased sperm binding up to normal levels (≥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. [ABSTRACT FROM AUTHOR]

BACKGROUND The aim of this study was to determine the relationship between human sperm hyperactivation (HA), sperm–zona pellucida (ZP) binding and the ZP-induced acrosome reaction (AR) of ZP-bound sperm in vitro. METHODS Sperm samples from 129 infertile men were studied. Motile sperm (2 × 106) selected by Pure sperm were incubated with four oocytes in 1 ml human tubal fluid supplemented with 10% human serum. After 2-h incubation, the number of sperm bound to the ZP and the AR of ZP-bound sperm were examined. Velocities and HA of sperm in insemination medium were assessed by Hamilton-Thorn Sperm Analyzer. RESULTS The HA was highly correlated with the ZP-induced AR in all the subjects (rho = 0.626, P P CONCLUSIONS The correlation of HA with the ZP-induced AR of ZP-bound sperm suggests a mechanistic link between HA and the physiological AR in humans. Assessment of HA of capacitated sperm in vitro may be a useful clinical test for male infertility associated with defective ZP-induced AR that does not require the use of human oocytes. [ABSTRACT FROM AUTHOR]