LAUSR

Abnormal sperm parameters such as oligospermia, asthenospermia, and teratozoospermia result in male factor infertility. Previous studies have shown that mitochondria play an important role in human spermatozoa motility. But the related pathogenesis is far from elucidated. The aim of this study was to investigate the association between GRIM-19 and asthenospermia. In this study, GRIM-19 knockout model (GRIM-19+/- mouse) was created through genome engineering. We showed that compared with WT mice, the sperm count and motility of GRIM-19+/- mice were significantly reduced. GRIM-19 may participate in the impact on sperm count and vitality by influencing the mitochondrial membrane potential, intracellular ROS production and increasing cell apoptosis. The spermatogenic cells of all levels in the lumen of the seminiferous tubules were sparsely arranged, and the intercellular space became larger in the testis tissue of GRIM-19+/- mice. The serum testosterone concentration is significantly reduced in GRIM-19+/- mice. The expression of steroid synthesis-related proteins StAR, CYP11A1 and 3β-HSD were decreased in GRIM-19+/- mice. To further confirm whether changes in testosterone biosynthesis were due to GRIM-19 downregulation, we validated this result using Leydig cells and TM3 cells. We also found that Notch signaling pathway was involved in GRIM-19-mediated testosterone synthesis to some extent. In conclusion, we revealed a mechanism underlying GRIM-19 mediated spermatozoa motility and suggested that GRIM-19 affected the synthesis of testosterone and steroid hormones in male mouse partly through regulating Notch signal pathways.