Progesterone-evoked increases in sperm [Ca²⁺]i correlate with the egg penetrating 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 with routine semen parameters and sperm fertilizing ability. Design: Baseline and P-evoked increases in [Ca²⁺]i of fresh versus capacitated human sperm were measured for known fertile donors and infertile men and compared with the results of semen analysis and in vitro penetration of zona-free hamster eggs. Setting: Andrology laboratory in a university hospital. Patients: Infertile men undergoing semen analysis. Interventions: Capacitation of spermatozoa and exposure of sperm to P (1 μg/mL). Main Outcome Measures: [Ca²⁺]i as measured using fura-2, percent zone-free hamster eggs penetrated, and number of penetrating sperm per egg. Results: Steady state [Ca²⁺]i increased from 74 ± 32 nM to 166 ± 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 dose-dependent manner. Progesterone-evoked calcium responses of sperm varied between different ejaculates of the same fertile donor and correlated 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 penetrating ability for individual infertile men. Conclusion: Progesterone-evoked increases in [Ca²⁺]i in motile capacitated spermatozoa cannot be used to discriminate between dysfunctional spermatozoa and those capable of penetrating eggs.