A sperm ion channel required for sperm motility and male fertility

Abstract

Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca²⁺-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca²⁺-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper^-/- mice, and CatSper^-/- sperm are unable to fertilize intact eggs. In addition, 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 motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women.