Hexavalent Chromium Inhibits Human Sperm Motility by Targeting Lysine Glutarylation and Mitochondrial Function

ABSTRACT Hexavalent chromium [Cr (VI)] is employed across a broad spectrum of manufacturing processes, resulting in considerable environmental contamination. Cr (VI) has the capacity to accumulate in spermatogonial stem cells, adversely affecting male reproductive function. However, the precise effects of Cr (VI) on human sperm function and the associated mechanisms remain inadequately characterized. We postulated that Cr (VI) impairs human sperm function by disrupting lysine glutarylation and mitochondrial function. This study demonstrates that exposure to K 2 CrO 4 leads to a reduction in sperm lysine glutarylation levels, an increase in intracellular reactive oxygen species (ROS), mitochondrial depolarization, and a decrease in ATP content. Notably, the administration of sodium glutarate, a precursor of glutaryl‐CoA, was observed to partially alleviate the detrimental effects of K 2 CrO 4 on lysine glutarylation levels, mitochondrial function, and sperm motility. Collectively, these findings substantiate our hypothesis that the impairment of human sperm motility induced by Cr (VI) is mediated through interfering with lysine glutarylation and mitochondrial function.