Defective protein kinase A and C pathways are common causes of disordered zona pellucida (ZP)–induced acrosome reaction in normozoospermic infertile men with normal sperm-ZP binding

Objective To determine association between defective protein kinases C (PKC) and A (PKA) and disordered zona pellucida (ZP)–induced acrosome reaction (DZPIAR) in normozoospermic infertile men with normal sperm-ZP binding. Design Sperm from DZPIAR infertile men were treated without (control) or with (test) phorbol myristate acetate (PMA, PKC activator) or dibutyryl cyclic AMP (dbcAMP, PKA activator) under in vitro standard culture condition. The ZP-induced AR was assessed and compared between control and test. Setting Public and private hospital–based clinical assisted reproduction technology (ART) centers. Patient(s) A total of 51 DZPIAR infertile men were involved in this study. Intervention(s) None. Main Outcomes Measure(s) Sperm-ZP binding and the ZP-induced IAR. Result(s) Both PMA and dbcAMP enhanced ZP-induced AR up to a normal level (≥25%) in some subjects with DZPIAR: 29 (57%) with PMA and 27 (53%) with dbcAMP. Overall 35 (69%) had the ZP-induced AR enhanced to normal by PMA or dbcAMP but 16 (31%) had little or no response to either agent. Fourteen men responded to the two activators differently: 8 effective only with PMA and 6 effective only with dbcAMP. Conclusion(s) Defective upstream of PKC and PKA pathways are highly associated with disordered ZPIAR in normozoospermic infertile men with normal sperm-ZP binding.