Inhibition of p38MAPK signal pathway alleviates radiation-induced
testicular damage
Abstract
Background and Purpose: How to prevent the damage of ionizing radiation
to testis has become an urgent problem to be solved. The present aim is
to investigate whether inhibition of p38MAPK signaling can alleviate
radiation-induced testicular damage. Experimental Approaches: HE
staining was used to measure the morphological changes of epididymis and
testis. Immunohistochemistry staining was used to assess the expression
of PLZF, SOX9, p-p38MAPK. RNA-Seq was used to profile gene expression.
The expression of Mapk14, Atf2, Ddit3 and Ap1m1 genes was detected by
qPCR. Western blotting was used to detect the protein expression of
p38MAPK and p-p38MAPK. Key Results: There was a dose-response
relationship between testicular injury and ionizing radiation. The sperm
quality was significantly decreased at 6 and 8 weeks after 6Gy of
radiation. Radiation led to the decrease of PLZF+ cells and increase of
SOX9+ cells in testis. RNA-Seq data showed radiation induced 969 genes
changed in the testis. The expression of genes related to p38MAPK signal
pathway enriched by GO was significantly increased by qPCR. The
expression of p-p38MAPK in testis was significantly increased at 4 weeks
after irradiation. SB203580 treatment increased numbers of spermatozoa,
the area and diameter of seminiferous tubules and numbers of SOX9+ cells
in irradiated mice, which were consistent with the increased sperm
movement rate and density under radiation with SB203580 administration.
Conclusions and Implications: Ionizing radiation significantly changes
testicular gene expression, in which p38MAPK signal pathway is
activated. p38MAPK inhibitor SB203580 partially alleviates the
testicular damage caused by radiation and accelerate the recovery of
sperm quality.