Enhancement of zona binding using 2-hydroxypropyl-β-cyclodextrin

Since membrane cholesterol depletion is known to play an important role in sperm capacitation, we have investigated the effect of 2-hydroxypropyl-beta-cyclodextrin, a cyclic oligosaccharide that mediates cholesterol efflux, on sperm functions. Sperm treatment with cyclodextrin did not affect the motility patterns but induced an increase in sperm binding to zona pellucida (24 +/- 5 versus 13 +/- 4 in control P < 0.01). Cyclodextrin treatment was associated with an increase in spontaneous acrosome reaction (32 +/- 8% versus 22 +/- 4% in controls after a 4 h incubation, P < 0.05; 61 +/- 10% versus 50 +/- 11% in controls after a 24 h incubation, NS) but with a decrease in acrosome response to ionophore challenge (44 +/- 5% versus 51 +/- 3% in controls, P < 0.05). Concerning cell sterols, cyclodextrin induced a rapid and dramatic fall in the cholesterol and desmosterol content of spermatozoa. We conclude that cyclodextrin is a powerful capacitating agent, but since it induces an increase in spontaneous acrosome loss, it needs to be further evaluated before routine use in assisted reproductive technology media.