Effects Of Subchronic Exposure On Reproductive System Of Adult Male Rats And Preliminary Mechanism Study

Objective:With the development of nanotechnology,nanomaterials have been immersed in all aspects of our lives.As an important nanomaterial,nano copper is widely used,including animal feed additives and drug delivery.Subchronic exposure to nano copper has been studied in liver,kidney,spleen,brain and ovary,but less in male reproductive system.Therefore,in this study,the effects of nano copper on the reproductive system of male rats were studied from the aspects of body weight change,sexual hormone secretion,testicular histomorphology change,sperm quality,sperm deformity rate and Cu element accumulation after sub chronic exposure of nano copper.By studying the changes of oxidative stress,Akt/mTOR,apoptosis and autophagy signaling pathway in testis after exposure to nano-copper,the mechanism of reproductive toxicity induced by nano-copper in male rats was preliminarily explored.Methods:1/10,1/20 and 1/40 nano-copper LD₅₀were used as low,middle and high dose groups respectively to establish nano-copper 28 days oral subchronic exposure model.The accumulation of copper in testis and blood was detected by ICP-MS.The body weight and organ coefficient of testis,histopathological changes,sperm viability,survival rate,number and sperm deformity rate,fructose content in testis,sex hormone（FSH,LH,T）level and testis were measured.The levels of oxidative stress,apoptosis,autophagy and Akt/mTOR signaling pathway were detected at gene and protein levels.Results:The body weight of rats decreased and testicular organ index increased after subchronic exposure to nano copper for 28 days.The results showed that the content of Cu in testis of rats did not accumulate.Compared with the control group,the subchronic exposure of nano copper decreased the sperm quality,increased the rate of sperm deformity,induced abnormal changes in testicular tissue structure,decreased fructose content,decreased sexual hormone secretion,and increased oxidative stress level in testicular tissue.The results of qRT-PCR and WB showed that nano copper could activate autophagy and apoptosis signaling pathway,and inhibit the expression of Akt/mTOR signaling pathway.Conclusion:The subchronic exposure of nano-copper can affect the growth,testis organ index and sex hormone secretion of rats,and has obvious damage effect on testicular tissue and sperm quality;the subchronic exposure of nano copper can induce testis oxidative stress,inhibit the expression of Akt/mTOR signaling pathway,activate cell autophagy and apoptosis signaling pathway,and cause damage to spermatogenesis through signaling cascade reaction.The negative effects can cause testicular tissue and sperm quality damage.