title: Ketamine inhibits human sperm function by Ca(2+)-related mechanism.
abstract: 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 ([Ca(2+)]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 Ca(2+) channel, CatSper, which modulates Ca(2+) 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 [Ca(2+)]i through inhibition of CatSper channel.
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, 330031, PR China; Department of Laboratory Animal Science, Nanchang University, Nanchang, 330006, PR China.
authors.forename: Yuanqiao
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, 330031, PR China.
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Anesthesiology, Jiangxi Province Tumor Hospital, Nanchang, 330029, PR China.
authors.forename: Bingda
authors.initials: B
authors.lastname: Li
authors.affiliation: Reproductive Medical Center, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, PR China.
authors.forename: Houyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Du
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, 330031, PR China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Weng
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, 330031, PR China. Electronic address: luotao@ncu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Institute of Life Science, Nanchang University, Nanchang, 330031, PR China. Electronic address: zengxuhui@ncu.edu.cn.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zeng
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology; D000778:Anesthetics, Dissociative / Q000008:administration & dosage; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; D002118:Calcium
keywords: Acrosome reaction; CatSper; Ketamine; Sperm motility; [Ca(2+)](i)