Extracellular ATP is a trigger for the acrosome reaction in human spermatozoa.

We tested the effect of extracellular adenosine 5'-triphosphate (ATPo) on the activation of human spermatozoa. ATPo, in a concentration range from 50 microM to 5 mM, induced the acrosome reaction, which, at the optimal concentration of 2.5 mM, was maximal (30-35% of spermatozoa activated) within 60 min of the addition of the nucleotide. At the end of this incubation in the presence of ATPo no decrease in cell motility and viability was observed. Among other purine/pyrimidine nucleotides only the ATP analogue adeny-5'-lyl imidodiphosphate was effective (70% of ATP); a weak (10% of ATP) effect was also observed with CTP and the ATP analogues adenosine 5'-(beta gamma-methylene)triphosphate and adenosine 5'-O-(thiotriphosphate). ATPo did not cause Ca2+ release from intracellular stores, nor it caused Ca2+ influx from the extracellular milieu; on the contrary, it caused a clear, albeit slow, plasma membrane depolarization. ATPo-activated spermatozoa showed a nearly 100% success rate in the standard hamster egg fertilization test. Our results describe a new effect of ATPo in human spermatozoa with relevant potential applications in fertility studies.