Ca2+ homeostasis and male fertility: a target for a new male contraceptive system

Ca 2+ is a key secondary messenger that determines sperm motility patterns. Mammalian sperm undergo capacitation, a process to acquire fertilizing ability, in the female reproductive tract. Capacitated sperm change their flagellar waveform to develop hyperactivated motility, which is crucial for successful sperm navigation to the eggs and fertilization. The sperm-specific channel, CATSPER, and an ATPase transporter, PMCA4, serve as major paths for Ca 2+ influx and efflux, respectively, in sperm. The ionic paths coordinate Ca 2+ homeostasis in the sperm, and their loss-of-function impairs sperm motility, to cause male infertility. In this review, we summarize the physiological significance of these two Ca 2+ gates and suggest their potential applications in novel male contraceptives.