Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping Review
Marie Twambaze, Ismail Adebayo, Saidi Odoma, Abdullateef Alagbonsi
Abstract
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: ) 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.