The chemosensing role of CatSper in mammalian sperm: an updated review

After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. Thus, the response of sperm to environmental factors is vital for successful fertilization. The cation channel of sperm (CatSper) is a sperm-specific, pH-sensitive, and Ca2+-permeable ion channel. It is responsible for the predominant Ca2+ entry in mammalian sperm and is involved in nearly every event of sperm to acquire fertilizing capability. CatSper also serves as a pivotal polymodal chemosensor in mammalian sperm by responding to multiple chemical cues. Physiological ligands (such as progesterone, prostaglandins, β-defensins, and odorants) provoke Ca2+ entry into sperm by activating CatSper and thus triggering sperm functions including hyperactivation, capacitation, the acrosome reaction, and chemotaxis. Additionally, synthetic and natural chemicals (such as medicines, endocrine disrupting chemicals, drugs of abuse, and antioxidants) affect sperm functions by regulating CatSper-dependent Ca2+ signaling. Therefore, understanding the interactions between CatSper and extracellular ligands sheds light on the mechanisms underlying male infertility and offers innovative diagnostic and treatment approaches. This underscores the importance of CatSper as a crucial regulatory target in male reproduction, linking sperm function with the extracellular environment. This review comprehensively summarizes the relevant studies describing the environmental factors that affect CatSper in humans and rodents.