Inhibition of p38MAPK signalling pathway alleviates radiation‐induced testicular damage through improving spermatogenesis

Abstract Background and Purpose Damage to the testis following exposure to ionizing radiation has become an urgent problem to be solved. Here we have investigated if inhibition of p38 mitogen‐activated protein kinase (p38MAPK) signalling could alleviate radiation‐induced testicular damage. Experimental Approach In mice exposed to whole body radiation (2‐6 Gy), morphological changes of the epididymis and testis was measured by histochemical staining. immunohistochemical and immunofluorescence procedures and western blotting were used to monitor expression and cellular location of proteins. Expression of genes was assessed by qPCR and RNA‐Seq was used to profile gene expression. Key Results Exposure to ionizing radiation induced dose‐dependent damage to mouse testis. The sperm quality decreased at 6 and 8 weeks after 6 Gy X‐ray radiation. Radiation decreased PLZF + cells and increased SOX9 + cells, and affected the expression of 969 genes, compared with data from non‐irradiated mice. Expression of genes related to p38MAPK were enriched by GO analysis and were increased in the irradiated testis, and confirmed by qPCR. Levels of phospho‐p38MAPK protein increased at 28 days after irradiation. In irradiated mice, SB203580 treatment increased spermatozoa, SOX9 + cells, the area and diameter of seminiferous tubules, sperm movement rate and density. Furthermore, SB203580 treatment increased SCP3 + cells, accelerating the process of spermatogenesis. Conclusion and Implications Exposure to ionizing radiation clearly changed gene expression in mouse testis, involving activation of p38MAPK signalling pathways. Inhibition of p38MAPK by SB203580 partly alleviated the testicular damage caused by radiation and accelerated the recovery of sperms through promoting spermatogenesis.