pH-dependent Ca oscillations prevent untimely acrosome reaction in human sperm.

During transit through the female reproductive tract, sperm encounter metabolites and environmental conditions that modulate various processes leading to fertilization. Intracellular Ca dynamics regulate the acrosome reaction (AR), which involves exocytosis of the acrosomal granule, a prerequisite for successful fertilization. We explored the ability of progesterone, prostanglandin-E1, and GABA to induce Ca mobilization and AR in single human spermatozoa capacitated under external pH (pH) conditions found in different regions of the female reproductive tract (pH 6.5, 7.4 and 8.0). The highest percentage of AR induction, regardless of the inducer, occurred when sperm were capacitated at pH 7.4. Interestingly, at pH 6.5 a high percentage of cells exhibit Ca oscillations, which prevent AR. These oscillations involve extracellular and intracellular Ca channels. Pharmacological inhibition of Ca oscillations restores the ability of spermatozoa to undergo the AR when exposed to progesterone, even if capacitated at pH 6.5.