Involvement of Ca2+ and ROS signals in nickel-impaired human sperm function

Abstract

As one of the main environmental pollutants and occupational hazards, nickel has been reported to have mutagenic, carcinogenic, and teratogenic properties, as well as reproductive toxicity. However, how nickel affects human reproduction is still unclear. In this study, the toxicity of nickel on human sperm and the underlying mechanisms were evaluated in vitro. We found that NiCl₂ (10, 50, and 250 μM) impaired sperm total motility and progressive motility in a dose- and time-dependent manner. In addition, sperm hyperactivation and the ability of human sperm to penetrate a viscous medium were found to be compromised after nickel exposure. Mechanically, NiCl₂ significantly inhibited the basal intracellular Ca²⁺ signaling. Besides, reactive oxygen species (ROS), superoxide, and malondialdehyde levels were increased in human sperm after exposure to different concentrations of NiCl₂. Consistently, eliminating excess ROS by N-acetyl-L-cysteine or tocopherol significantly alleviated nickel-impaired sperm motility. Taken together, these results revealed that nickel could compromise sperm functions by interfering with Ca²⁺ signaling and inducing excessive oxidative stress. These findings suggest that, in the high and occupational nickel exposure environments, the contribution of nickel toxicity to the males who wish to preserve their fertility is worthy of careful evaluation.

Keywords: Ca(2+) signaling; Nickel; Progesterone; ROS; Sperm function.