pH-dependent Ca⁺² 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 Ca²⁺ 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 Ca²⁺ mobilization and AR in single human spermatozoa capacitated under external pH (pH_e) conditions found in different regions of the female reproductive tract (pH_e 6.5, 7.4 and 8.0). The highest percentage of AR induction, regardless of the inducer, occurred when sperm were capacitated at pH_e 7.4. Interestingly, at pH_e 6.5 a high percentage of cells exhibit Ca²⁺ oscillations, which prevent AR. These oscillations involve extracellular and intracellular Ca²⁺ channels. Pharmacological inhibition of Ca²⁺ oscillations restores the ability of spermatozoa to undergo the AR when exposed to progesterone, even if capacitated at pH_e 6.5.