Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping Review.

BACKGROUND

Calcium channels are critical regulators of spermatogenesis and sperm functions, orchestrating processes like motility, capacitation, and fertilization. Their dysfunction is linked to male infertility, contributing to approximately 50% of infertility cases globally. This scoping review synthesizes evidence on the role of calcium channels in male fertility, focusing on their physiological mechanisms and implications for reproductive health.

METHODS

Following the PRISMA-ScR checklist and Arksey and O'Malley's framework, a search of PubMed, Scopus, and Web of Science identified 978 records from January 2000 to July 2025. After screening, 142 peer-reviewed studies on mammalian models were included. Data were extracted on channel types, study designs, and outcomes, categorized by the physiological functions of sperm.

RESULTS

The review identified five channel-mediated regulators of sperm calcium, including CatSper, voltage-dependent calcium channels (VDCCs), TRP channels, inositol triphosphate (IP3) and ryanodine receptors (IP3Rs & RyRs), and calcium-sensing receptor (CaSR), as key players in sperm motility, capacitation, and fertilization. About 19 non-channel mediators of sperm calcium were also reported.

CONCLUSION

Calcium channels are pivotal to male fertility and contraceptives, offering diagnostic and therapeutic potential. Future research should focus on multi-channel interactions, human-based studies, and environmental impacts to enhance fertility treatments and develop non-hormonal contraceptives.