The effect and mechanism of Grim 19 on mouse sperm quality and testosterone synthesis. Issue 6 (19th May 2022) - Zhao, Yue
Abstract : 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 gene associated with retinoid-interferon-induced mortality 19 (GRIM19) and asthenospermia. In this study, Grim19 knockout model ( Grim19+/− mouse) was created through genome engineering. We showed that compared with WT mice, the sperm count and motility of Grim19+/− mice were significantly reduced. Grim19 may contribute to sperm count and vitality by influencing the mitochondrial membrane potential, intracellular reactive oxygen species 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 Grim19+/− mice. The serum testosterone concentration is significantly reduced in Grim19+/− mice. The expression of steroid synthesis-related proteins STAR, CYP11A1, and HSD3B was decreased in Grim19+/− mice. To further confirm whether changes in testosterone biosynthesis were due to Grim19 downregulation, we validated this result using Leydig cells and TM3 cells. We also found that Notch signaling pathway was involved in Grim19 -mediated testosterone synthesis to some extent. In conclusion, we revealed a mechanism underlying Grim19 mediated spermatozoa motility and suggested that Grim19 affected the synthesis of testosterone and steroid hormones in male mouse partly through regulating Notch signal pathways.