The Crosstalk Of Autophagy And Apoptosis In Cadmium-induced Injury/recovery Of Male Reproduction In Rats

Part ?.Effects of cadmium exposure on reproductive system injury and recovery in adult male SD ratsObjectives:The research explores the effects of cadmium exposure on reproductive system injury and repair in adult male SD rats.Methods:102 adult SD male rats were randomly divided into four groups,which were treated with Cd(0,0.2,0.4,0.8mg/kg/d for 5 consecutive weeks)by intraperitoneal injection.The examination endpoints in each group was different(shown in Fig.1):Four endpoints in Group 1(0.9%Nacl)were designed on Week 1,5,8,13 respectively.Three endpoints in Group 2(0.2mg/kg Cdcl2)and Group 3(0.4mg/kg Cdcl2)were on Week 5,8 and 13.Seven endpoints in Group 4(0.8mg/kg Cdcl2)were on Week 1,2,3,4,5,8 and 13.All endpoints are detected on the body weight and organ coefficient,sperm count and motility,cadmium content in testis,testicular histopathology,testicular marker enzyme activity,and oxidative stress detection.Results:Cadmium exposure for 5 consecutive weeks resulted in the continuous accumulation of cadmium in the testes,which affected the body weight and organ coefficient.Cadmium induced oxidative stress and lowered testicular enzyme activity.Then,the morphology of testicular tissue was damaged,resulting in a significant decrease of sperm counts and vitality.After one cycle of spermatogenesis 8 weeks without cadmium exposure(ie.At the end of 13th week),oxidative stress is decreased,and the structures of seminiferous tubules are recovered,and toxic effects are ameliorated in epididymal sperm compared with that at the end of 5th week.Conclusions:Cadmium exposure induces male reproductive lesions via eliciting oxidative stress,lowering testicular enzyme activity in Sertoli cell and germ cell and reducing semen quality.After one cycle of spermatogenesis 8 weeks without cadmium exposure,some reproductive injury has recovered,which indicates that the testis has some self-repair function.Part ?.The role of autophagy and apoptosis in cadmium-induced testicular injury/recovery in ratsObjective:To further explore the molecular mechanism of cadmium-induced testicular injury in rats from the perspective of autophagy and apoptosis based on the first part of the experiment.Methods:102 adult SD male rats were randomly divided into four groups,which were treated with Cd(0,0.2,0.4,0.8mg/kg/d for 5 consecutive weeks)by intraperitoneal injection.The examination endpoints in each group was different(shown in Fig.1):Four endpoints in Group 1(0.9%Nacl)were designed on Week 1,5,8,13 respectively.Three endpoints in Group 2(0.4mg/kg Cdcl2)and Group 3(0.4mg/kg Cdcl2)were on Week 5,8 and 13.Seven endpoints in Group 4(0.8mg/kg Cdcl2)were on Week 1,2,3,4,5,8 and 13.All endpoints are detected on the expression of autophagy marker protein(LC3,BECLIN1,p62,mTOR,p-mTOR)in testis,TUNEL assay and ultrastructure of Sertoli cells,Ley dig cells,spermatogenium,primary spermatocytes,secondary spermatocytes on electron microscopy.Results:Cadmium exposure increased protein levels of LC3B-?,BECLIN1,and decreased protein level of p62,p-mTOR.Followed by the augment of testicular cells apoptosis,cadmium induced autophagy in Sertoli cells,Leydig cells,and germ cells.After one cycle of spermatogenesis 8 weeks without cadmium exposure(ie.At the end of 13th week),protein levels of LC3B-?,BECLIN1 were fortified,and protein level of p62,p-mTOR were lessened;Furthermore,the ultrastrmcture of testicular cells revealed that autophagy was reduced and mainly in the Sertoli cells.Conclusions:Cadmium induces autophagy and apoptosis in testicular cells via restraining mTOR pathway in rats.In reparative phase,autophagy is signicantly diminished.These results suggest that this may be due to the fact that cadmium-initiated strong autophagy promotes apoptosis and kills cells,while mild autophagy antagonizes apoptosis and protects cells.