Modulation of sperm tail protein tyrosine phosphorylation by pentoxifylline and its correlation with hyperactivated motility

Abstract

Objective: To assess the effect of pentoxifylline on human sperm functions that are crucial to fertilization. Design: Prospective, controlled study. Setting: Academic tertiary care institute. Patient(s): Healthy male sperm donors. Intervention(s): The effects of pentoxifylline (3.6 mM) on hyperactivated motility, sperm binding to the zona pellucida, and sperm protein tyrosine phosphorylation were evaluated. Main Outcome Measure(s): Hyperactivated motility was assessed by computer-assisted motion analysis, and tight binding of sperm to homologous zonae pellucidae was examined using the hemizona assay. Sperm protein phosphorylation was evaluated using indirect immunofluorescence with an antibody to phosphotyrosine (PY20). Result(s): Pentoxifylline significantly stimulated hyperactivated motility at 1 hour and 4 hours; it also significantly increased sperm binding to the zona pellucida and enhanced sperm tail tyrosine phosphorylation at 4 hours under capacitating conditions. There was a statistically significant correlation between hyperactivated motility and sperm tail protein phosphorylation. Conclusion(s): Pentoxifylline stimulates sperm functions that are essential to achieving fertilization under in vitro conditions in sperm obtained from fertile men. The enhancement of hyperactivated motility is associated with the stimulation of sperm tail tyrosine phosphorylation, suggesting a causal relation and the involvement of a modulatory effect after cyclic adenosine monophosphate–dependent phosphorylation of intermediate proteins.