Electrolyte Homeostasis in Sperm Biology and Channelopathies in Male Infertility: A Scoping Review

Despite extensive research, a consolidated synthesis of electrolyte regulation and related channelopathies in sperm biology remains limited. This scoping review maps global evidence on ionic homeostasis and male fertility.

Following PRISMA-ScR guidelines, searches were conducted in PubMed, Scopus, and Web of Science for studies published between January 2000 and August 2025. A total of 210 studies were reviewed.

Publications were dominated by China (25.71%), Nigeria (8.57%), and the United States (8.57%), followed by Egypt (5.24%), Germany (4.76%), India (4.29%), and Spain (4.29%), with additional contributions from more than 30 countries spanning Europe, Asia, Africa, and the Americas. Core ion channels, including CatSper, SLO3, TRPV6, CFTR, ClC-2, Na⁺/H⁺ exchangers, and aquaporins, were consistently associated with pH regulation, calcium signaling, and membrane potential essential for fertilization. Mutations in the CFTR, ADGRG2, TRPV6, and SLO3 genes were implicated in congenital or idiopathic infertility. Environmental, metabolic, and toxicological stressors, including heavy metals and oxidative imbalance, disrupted ionic homeostasis and impaired sperm quality.

Ion-channel regulation and electrolyte balance are essential for sperm function. Integrating genetic, physiological, and toxicological evidence highlights key biomarkers and therapeutic targets, emphasizing the need for channel-focused interventions and broader global research representation.