Intracellular Calcium Accumulation and Responsiveness to Progesterone in Capacitating Human Spermatozoa

Abstract

ABSTRACT: Progesterone induced a rapid, long‐lasting, dose‐dependent increase of intracellular free calcium concentration ([Ca2 +]i) in human sperm capacitated overnight. This effect was not counteracted by the cytosolic progesterone receptor antagonist RU486 (1 μmol/L) nor by the GABA‐A receptor antagonists bicuculline (10 μmol/L) and picrotoxin (50 μmol/L). Also, the rank order of potency of several progestative steroids on [Ca2 +]i differed from that previously reported for uterine intracellular progesterone receptor or for P‐GABA interaction in the central nervous system, indicating a different pathway for progesterone stimulation of human sperm. Modifications of basal and progesterone‐stimulated [Ca2 +]i during sperm capacitation were also studied. A progressive, parallel increase of basal and progesterone‐stimulated [Ca2 +]i in capacitating spermatozoa was found. In particular, progesterone‐stimulated [Ca2 +]i increased from a basal concentration of 147% ± 17% at 10 minutes to 327% ± 65% after 120 minutes of incubation in capacitating medium. This increase was well correlated with basal [Ca2 +]i (r = 0.93). In contrast, basal and progesterone‐stimulated [Ca2 +]i concentrations were constantly low in spermatozoa incubated in noncapacitating medium. In capacitated spermatozoa, initial responsiveness to progesterone and basal [Ca2 +]i was higher than in capacitating and noncapacitated samples, and remained constant throughout the duration of the experiment. The progressive, parallel increase of [Ca2 +]i and response to progesterone observed during in vitro capacitation of human spermatozoa might be physiologically relevant in vivo during capacitation of sperm in the female genital tract.