The effect of ISRIB on LPS-induced spermatogenic dysfunction in mice
Aim To explore the effect of ISRIB on lipopolysaccharide(LPS)-induced spermatogenic dysfunction in mice and its relevant mechanism.Methods 27 ICR mice were randomly divided into a control group,a model group,and a model+IS-RIB group.A single intraperitoneal injection of LPS was used to establish the spermatogenic dysfunction mice model.The mass,sperm count,and sperm deformity rate of testicles and epididymal tail in each group were compared.HE staining was used to detect testicular morphology and structure.Real-time PCR was used to detect the level of inflammatory factors interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α.The biochemical reagent kits were used to detect the levels of malondialdehyde(MDA),gluta-thione(GSH),and oxidized glutathione(GSSG)in the testes.Results In model mice,LPS caused a decrease in sperm count and an increase in sperm deformity rate(P<0.001),the morphology and structure of the testes were disrupted,the seminiferous tu-bules shrink,the diameter of the lumen became smaller,the arrangement of spermatogenic cells at all levels was disordered,and the number of sperm in the lumen was decreased,inflammatory factor IL-1,IL-6 and TNF-α were elevated(P<0.05,P<0.0001);GSH was decreased,MDA and GSSG increased(P<0.01),and GSH/GSSG decreased(P<0.001).After ISRIB intervention,the num-ber of sperm,deformity rate,and testis morphological structure of model+ISRIB group mice were improved,and there was a trend of improvement in inflammatory factors and oxidative stress(P<0.05).Conclusion ISRIB alleviated LPS-induced spermatogenic dysfunction in mice,which may be partially due to the decrease of oxidative stress level in testis.