A sperm ion channel required for sperm motility and male fertility

Calcium and cyclic nucleotides have crucial roles in mammalian fertilizatio n, but the molecules comprising the Ca2+-permeation pathway in sperm motili ty are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-tr ansmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repe at structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in o therwise normal mice. Sperm motility is decreased markedly in CatSper(-/-) mice, and CatSper(-/-) sperm are unable to fertilize intact eggs. In additi on, the cyclic-AMP-induced Ca2+ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm mo tility and fertilization. CatSper represents an excellent target for non-ho rmonal contraceptives for both men and women.