Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping
Marie Francoise Twambaze1, Ismail Abiola Adebayo2, Saidi Odoma3
1Department of Pharmacy, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda.
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.
Related Concept Videos
01:27Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
01:22Birth Control Methods
01:17Antiepileptic Drugs: Calcium Channel Blockers
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
01:22Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...