Acrosomal exocytosis is compromised in CATSPER1 KO mouse sperm

In brief Catsper is an essential calcium channel for sperm capacitation; however, its role in acrosomal exocytosis has not been fully elucidated. This study shows that the lack of Catsper channels in mouse sperm alters the normal occurrence of exocytosis. Abstract Catsper is a Ca 2+ -selective channel localized in the principal piece of the sperm flagellum. Although its fundamental role in capacitation, an essential process required for fertilization, has been widely demonstrated, its role in acrosomal exocytosis (AE) is not well established. Here, by using a combination of in vitro and in vivo experiments, we show that CATSPER1 KO sperm have impaired capacity to undergo AE when stimulated with low concentrations of progesterone (Prog) and persist even when more potent pharmacological agents, such as Thapsigargin or Ca 2+ ionophore A23187, were used. Furthermore, Thapsigargin evokes an intracellular Ca 2+ concentration increase in a lower number of sperm cells from CATSPER1 KO mice compared to those from CATSPER1 HET mice. In addition, CATSPER1 KO sperm displayed an altered intracellular pH alkalinization and were unable to achieve plasma membrane hyperpolarization during capacitation, a fundamental step to prepare the sperm for AE. The failure of CATSPER1 KO sperm to ascend through the female reproductive tract prevents observation of the AE process at its physiological site. Altogether, our results demonstrate the importance of Ca 2+ influx through Catsper channels for the occurrence of AE.