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

ABSTRACT

Ca²⁺ 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 Ca²⁺ influx and efflux, respectively, in sperm. The ionic paths coordinate Ca²⁺ 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 Ca²⁺ gates and suggest their potential applications in novel male contraceptives.

KEYWORDS:

• Ca²⁺
• sperm motility
• CATSPER
• PMCA4
• male contraception

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [RS-2023-00210046 to JYH; NRF-2021R1A2C1011456 to KL].