Effects of γ-aminobutyric acid on human sperm motility and hyperactivation

Abstract

This study was undertaken to evaluate the effects of gamma-aminobutyric acid (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system, and intracellular cAMP content in 22 normozoospermic semen samples. Because of the possible interaction of progesterone with the GABAA receptor, we also evaluated the effects of progesterone on these parameters. GABA increased beat cross frequency, curvilinear velocity (VCL), the percentage of spermatozoa moving with an average path velocity > 10 microns/s (active) and hyperactivation, and decreased linearity and straightness. Bicuculline, a GABAA receptor antagonist, antagonized the effects of GABA on all these parameters except the percentage of active spermatozoa. Muscimol, a GABAA receptor agonist, increased VCL, the percentage of active spermatozoa, and hyperactivation by about the same extent as GABA, suggesting the involvement of the GABAA receptor. However, the GABAB receptor also seems to mediate some of the effects of GABA, because baclofen, a selective agonist for this receptor, increased significantly the percentage of active spermatozoa and hyperactivation. The effect of baclofen on this latter parameter was, however, less pronounced than that obtained with GABA or muscimol. Progesterone had the same effects as GABA on sperm kinematic parameters and hyperactivation and the simultaneous presence of both compounds was not more effective than each single one. GABA and progesterone did not have any effect on intracellular cAMP content. In conclusion, GABA modulated sperm kinematic parameters and increased hyperactivation. These effects have the same magnitude of those produced by progesterone and seem to be mediated mainly by the GABAA receptor. We speculate that GABA may be a physiological regulator of sperm function.

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

“…S3, Bottom panels and Table S6). In capacitated spermatozoa, P4 stimulation increased VCL by 12%, comparable to numbers reported earlier (7,21), but VCL values remained unchanged in the presence of PregS, pristimerin, or lupeol alone (Fig. S3A, Top and Inset and Table S6).…”

Activation of GABAAReceptor/Cl−Channel and Capacitation in Rat Spermatozoa: HCO3−and Cl−are Essential

“…It has been shown that GABA increases capacitation in guinea pig and ejaculated human sperm and ram sperm [De las Heras et al 1997;Zhang et al 2000]. Moreover, GABA also increases hyperactivated motility in ejaculated human spermatozoa [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000]. Importantly, in some cases stimulation by a GABA A receptor agonist or inhibition by a GABA A receptor antagonist was also observed [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000].…”

“…Moreover, GABA also increases hyperactivated motility in ejaculated human spermatozoa [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000]. Importantly, in some cases stimulation by a GABA A receptor agonist or inhibition by a GABA A receptor antagonist was also observed [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000]. As discussed above, progesterone also increase capacitation and hyperactivated motility of ejaculated human and porcine sperm, but data linking the effect to the GBRCs have not been reported [Meizel 2004].…”

“…It has been shown that GABA increases sperm capacitation and hyperactivated motility in ram [De las Heras et al 1997], human [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000] and guinea pig [Zhang et al 2000]. Importantly, some of these studies also ascertained activation by a GBRC agonist or inhibition of the GABA effects by a GBRC antagonist [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000].…”

“…Importantly, some of these studies also ascertained activation by a GBRC agonist or inhibition of the GABA effects by a GBRC antagonist [Calogero et al 1996;Ritta et al 1998;Zhang et al 2000].…”