Progesterone triggers a wave of increased free calcium during the human sperm acrosome reaction

The mammalian sperm acrosome reaction (AR), an essential fertilization event, requires an influx of Ca2+. The Ca2+ increase occurring in the human sperm head during the AR initiated by progesterone, a putative in vivo AR initiator, was investigated using video-image analysis with fura-2, a fluorescent Ca2+ probe. Progesterone treatment of capacitated human sperm resulted in a wave-like increase in sperm head cytosolic [Ca2+]i that appears to increase fastest in a region near the equatorial segment and then spreads throughout the rest of the head. The progesterone-mediated Ca2+ increase in the sperm head was strongly inhibited and the wave eliminated by picrotoxin, a blocker of GABAA receptor/Cl- channels and an inhibitor of the progesterone-mediated Cl- efflux and progesterone-initiated AR of human sperm. These results are the first to detect a ligand-mediated Ca2+ wave in sperm and to suggest that Cl- efflux influences Ca2+ influx during the AR.