Human follicular fluid stimulates the sperm acrosome reaction by interacting with the γ-aminobutyric acid receptors

Objective: To evaluate whether gamma-aminobutyric acid receptors are involved in human sperm acrosome reaction induced by the follicular fluid (FF). Design: Random selection of normal sperm samples. Setting: Normal men in an university clinic of andrology. Patient(s): Men with normal sperm analysis parameters. Intervention(s): None. Main Outcome Measure(s): Acrosome reaction on motile spermatozoa. Result(s): Follicular fluid stimulated the acrosome reaction dose-dependently. The effect of a maximally effective concentration of FF (30%, vol/vol) was significantly suppressed by bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) receptor antagonist, added concomitantly. Each of the two antagonists used alone was devoid of effect. Because the GABA(A) receptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of the FF. Picrotoxin alone did not have any effect on the acrosome reaction induced by the FF, whereas it had a significant suppressive effect if coincubated with saclofen. The acrosome reaction induced by the FF was also inhibited by picrotoxin plus verapamil, a calcium channel blocker, whereas verapamil alone had no significant effect. This suggested that both chloride and calcium ions mediated the acrosome reaction induced by the FF. Conclusion(s): The simultaneous blockade of GABA(A) and GABA(B) receptors suppressed the acrosome reaction induced by the FF. This finding suggested that GABA receptors play a physiologic role in sperm activation and shed further light on the mechanism of FF action on human sperm acrosome reaction. (C) 2004 by American Society for Reproductive Medicine.