Ketamine inhibits human sperm function by Ca2+-related mechanism

Ketamine, a dissociative anesthetic, which was widely used in human and animal medicine, has become a popular recreational drug, as it can induce hallucinatory effects. Ketamine abuse can cause serious damage to many aspects of the organism, mainly reflected in the nervous system and urinary system. It has also been reported that ketamine can impair the male genital system. However, the detailed effect of ketamine on human spermatozoa remains unclear. Thus, we investigated the in vitro effects of ketamine on human sperm functions, to elucidate the underlying mechanism. Human sperm were treated in vitro with different concentrations of ketamine (0, 0.125, 0.25, 0.5, 1 g/L). The results showed that 0.25–1 g/L ketamine inhibited sperm total motility, progressive motility and linear velocity, in a dose-dependent manner. In addition, the sperm’s ability to penetrate viscous medium and the progesterone-induced acrosome reaction were significantly inhibited by ketamine. Ketamine did not affect sperm viability, capacitation and spontaneous acrosome reaction. The intracellular calcium concentration ([Ca2+]i), which is a central factor in the regulation of human sperm function, was decreased by ketamine (0.125–1 g/L) in a dose-dependent manner. Furthermore, the currents of the sperm-specific Ca2+ channel, CatSper, which modulates Ca2+ influx in sperm, were inhibited by ketamine (0.125–1 g/L) in a dose-dependent manner. Our findings suggest that ketamine induces its toxic effects on human sperm functions by reducing sperm [Ca2+]i through inhibition of CatSper channel. •Ketamine decreases human sperm motility.•Ketamine inhibits the progesterone-induced acrosome reaction of human sperm.•Ketamine lowers human sperm intracellular Ca2+ concentration.•Ketamine suppresses human sperm CatSper currents.