Type 5 phosphodiesterase regulation of human sperm motility

OBJECTIVE: Inhibition of phosphodiesterases results in the buildup of intracellular cyclic nucleotides, which have been shown to affect sperm motility and acrosome reaction. The objective of this study was to determine whether the cyclic guanosine monophosphate-specific type 5 phosphodiesterase inhibitor sildenafil has an effect on sperm motility and acrosome parameters. STUDY DESIGN: Sperm cells were washed by two-layer colloid wash and resuspended in modified human tubal fluid with 5% serum albumin. They were incubated in the presence of different concentrations (0-40 nmol/L) of the type 5 phosphodiesterase inhibitor sildenafil. Aliquots of sperm were removed at hours 0, 4, 24, and 48, and motility parameters were measured on the Hamilton-Thorn HTM-C (Hamilton-Thorn Research, Danvers, Mass) motility analyzer. Sperm acrosomes were analyzed with the Spermac (Stain Enterprises, South Africa; distributed by Sage Biopharma, Bedminster, NJ) acrosome stain. RESULTS: Sperm progressive motility and hyperactivation were stimulated to greater than the control at hour 4, followed by a decrease. There was a dose-dependent effect of the type 5 phosphodiesterase inhibitor on sperm motility parameters but not on percentage of cells with acrosome reaction. The type 5 phosphodiesterase inhibitor stimulated sperm acrosome reaction by almost 50% above the control. CONCLUSION: These results suggest that inhibition of type 5 phosphodiesterase activity in human sperm resulted in enhanced progressive motility and hyperactivation. In addition, inhibition of type 5 phosphodiesterase also caused an increase in acrosome reaction. This suggests a role for type 5 phosphodiesterase in preventing premature acrosome reaction, which is associated with failed fertilization.