Type 5 phosphodiesterase regulation of human sperm motility

OBJECTIVE: Inhibition of phosphodiesterases results in the buildup of intra cellular cyclic nucleotides, which have been shown to affect sperm motility and acrosome reaction. The objective of this study was to determine whethe r the cyclic guanosine monophosphate-specific type 5 phosphodiesterase inhi bitor sildenafil has an effect on sperm motility and acrosome parameters. STUDY DESIGN: Sperm cells were washed by two-layer colloid wash and resuspe nded in modified human tubal fluid with 5% serum albumin. They were incubat ed in the presence of different concentrations (0-40 nmol/L) of the type 5 phosphodiesterase inhibitor sildenafil. Aliquots of sperm were removed at h ours 0, 4, 24, and 48, and motility parameters were measured on the Hamilto n-Thorn HTM-C (Hamilton-Thorn Research, Danvers, Mass) motility analyzer. S perm acrosomes were analyzed with the Spermac (Stain Enterprises, South Afr ica; 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 dos e-dependent effect of the type 5 phosphodiesterase inhibitor on sperm motil ity parameters but not on percentage of cells with acrosome reaction. The t ype 5 phosphodiesterase inhibitor stimulated sperm acrosome reaction by alm ost 50% above the control. CONCLUSION: These results suggest that inhibition of type 5 phosphodiestera se activity in human sperm resulted in enhanced progressive motility and hy peractivation. In addition, inhibition of type 5 phosphodiesterase also cau sed an increase in acrosome reaction. This suggests a role for type 5 phosp hodiesterase in preventing premature acrosome reaction, which is associated with failed fertilization.