PROGESTERONE-EVOKED INCREASES IN SPERM [CA2+]I CORRELATE WITH THE EGGPENETRATING ABILITY OF SPERM FROM FERTILE BUT NOT INFERTILE MEN

Objectives: To investigate the relationship between sperm capacitation and intracellular calcium ([Ca2+]i) and to correlate these findings w ith routine semen parameters and sperm fertilizing ability. Design: Ba seline and P-evoked increases in [Ca2+]i of fresh versus capacitated h uman sperm were measured for known fertile donors and infertile men an d compared with the results of semen analysis and in vitro penetration of zona-free hamster eggs. Setting: Andrology laboratory in a univers ity hospital. Patients: Infertile men undergoing semen analysis. Inter ventions: Capacitation of spermatozoa and exposure of sperm to P (1 mu g/mL). Main Outcome Measures: [Ca2+]i as measured using fura-2, percen t zone-free hamster eggs penetrated, and number of penetrating sperm p er egg. Results: Steady state [Ca2+]i increased from 74 +/- 32 nM to 1 66 +/- 97 nM after capacitation, as did P-evoked peak and plateau [Ca2 +]i. Deletion of calcium from the assay buffer with ethylene-bis (oxy- ethylenenitriolo) tetraacetic acid abrogated the P-evoked increments. RU486, a P receptor antagonist, reduced the P-evoked response in a dos e-dependent manner. Progesterone-evoked calcium responses of sperm var ied between different ejaculates of the same fertile donor and correla ted with their egg penetrating ability. Sperm from infertile men with abnormal morphology exhibited lower egg penetrating ability and lower mean peak P-evoked [Ca2+]i than morphologically normal sperm. However, free intracellular calcium parameters correlated only weakly with pen etrating ability for individual infertile men. Conclusion: Progesteron e-evoked increases in [Ca2+]i in motile capacitated spermatozoa cannot be used to discriminate between dysfunctional spermatozoa and those c apable of penetrating eggs.