Progesterone and anandamide diminish the inhibitory effect of zinc on mature human sperm

Zinc ion (Zn2+) homeostasis is very important for sperm capacitation and hyperactivation. Zn2+ is a specific inhibitor of the voltage-dependent proton channel (Hv1). Intracellular alkalisation of human spermatozoa is mainly dependent on opening of Hv1. Anandamide may affect spermatozoa through activation of Hv1. An increase in intracellular pH and progesterone (P4) activate cation channels of spermatozoa (CatSper). This study was designed to elucidate the interaction between ZnCl2, P4 and anandamide on human sperm function and intracellular calcium concentrations ([Ca2+]i). Human normal semen samples (n = 30) were diluted (20 × 106 spermatozoa mL-1) and divided into control and ethanol (0.01%)-, anandamide (1 nM)-, ZnCl2 (1 mM)-, P4 (10µM)-, anandamide+ZnCl2- and P4+ZnCl2-treated groups. Sperm kinematics, viability, acrosome status and [Ca2+]i were assessed. The percentage of viable and motile spermatozoa and sperm velocity was reduced in the ZnCl2-treated groups. Anandamide and P4 attenuated the inhibitory effects of ZnCl2 on sperm kinematics. Loss of the acrosome membrane was observed in all experimental groups. P4 and anandamide are present naturally in secretions of the female reproductive tract and modulate the inhibitory effects of ZnCl2 on sperm kinematics. This attenuation is probably due to a change in [Ca2+]i and prevention of Hv1 inactivation by P4 and anandamide respectively.