The Early Prediction Research Of Reproductive Damage In Male SD Rats Induced By Anti-cancer Drugs

Objective:With the increasing development of new drugs,how to detect the potential toxicity of drugs,to improve drugs and avoid clinical risks has been the focus of researchers.In this study,the use of anti-cancer drugs with reproductive toxicity was used to model the changes in CABS1 and SP-2 under varying degrees of reproductive system injury,compared with the currently used male reproductive system damage detection indicator,to explore its early forecasting capabilities.Methods:The SD rats administrated with doxorubicin hydrochloride were divided into blank control group,7mg/m~2 group and 14mg/m~2 group,8 rats/groups,once every 21days administered intravenously for 3 times,and then they were killed one week after the last administration.The SD rats administrated with busulfan were divided into DMSO group,1.0 mg/kg group and 15 mg/kg group.5 rats/groups,injected intraperitoneally for one time,and they were killed after one month.Detection of drug safety evaluation experiment of common injury to male reproductive index:bilateral testis weight,diameter,bilateral epididymis weight,right cauda epididymis weight,sperm count,Motility,progressive,VAP,VSL,VCL,ALH,BCF,STR,LIN,serum testosterone and testicular histopathology,and detection of potential male QRT-PCR reproductive damage marker expression in the testis tissues of CABS1 and SP-2mRNA.Results:1.In the 7 mg/m~2 group of doxorubicin hydrochloride experiment,compared to the blank control group,the routine testis coefficient,in addition to the absolute weight and relative weight of testis(g/100gBW),the diameter of the left side is reduced,other indicators:weight,sperm count and Motility,progressive,average path velocity(VAP),straight-line velocity(VSL),curvilinear velocity(VCL),amplityde of lateral head displacement(ALH),beat/cross frequency(BCF),straightness(STR)and linearity(LIN),testicular tissue pathology and serum testosterone concentration was found no significant changes.CABS1mRNA expression in the testis tissues significantly was down.SP-2mRNA also had the downward trend.2.In the doxorubicin hydrochloride 14 mg/m~2 group,the body weight of the rats decreased,the absolute and relative weight of the testes,the bilateral lateral diameter,and the absolute and relative weight of the epididymis were significantly reduced,and sperm counts were significantly reduced.Sperm activity decreased significantly,testicles severely atrophied,and there was no statistical difference in serum testosterone levels.The expression of CABS1 mRNA and SP-2 mRNA was also significantly down-regulated in testis.3.In the busulfan 1.0 mg/kg group,in routine testing indicators such as rat body weight,absolute and relative weight of testis,bilateral lateral diameter,absolute and relative weight of epididymis,sperm count,Motility,progressive,VAP.There was no significant change in pathological structure and serum testosterone content in VSL,VCL,ALH,BCF,STR,LIN,testis,and the expression of CABS1 m RNA and SP-2 mRNA in the testis were down-regulated.4.In the busulfan 15.0mg/kg group,except for the absolute and relative weight loss of the rat testes,and the reduction of bilateral lateral diameter,the remaining indicators:absolute and relative weights of the epididymis,sperm counts,facilities,progressive,VAP,VSL There was no significant change in the histopathologic examination of VCL,ALH,BCF,STR,LIN,testicular tissue,and serum testosterone.The expression of CABS1 mRNA and SP-2 mRNA was significantly down-regulated in testis.Conclusions:1.The intravenous injection of doxorubicin hydrochloride once every 3 weeks,continuous injection of 3 cycles and a single intraperitoneal injection of busulfan caused damage to the reproductive system of male SD rats.2.In the male reproductive system injury model,the expression levels of CABS1 and SP-2 have been down-regulated when the conventional reproductive toxicity indicators have not changed.When the conventional detection indicators of reproductive toxicity change in different degrees,the expression levels of CABS1 and SP-2 have been significantly reduced.3.CABS1 and sp-2 have the potential to be the early biomarkers of male reproductive system damage.