The Study Of Male Reproductive Toxicity Induced By Nano-TiO₂

Objective:We used ICR male mice as experimental model to study the male reproductive toxicity of nano-TiO₂ in this research.Semen quality and histopathology changes were tested.The oxidative damage and the mRNA Sequencing changes of the testis induced by nano-TiO₂ were also studied in order to discuss the mechanisms of male reproductive toxicity caused by nano-TiO₂.Methods:1.60 normal male mice were randomly divided into four groups:control group,10 mg/kg BW nano-TiO₂ treatment group,50 mg/kg BW nano-TiO₂ treatment group,100 mg/kg BW nano-TiO₂ treatment group,with 15 male mice in each group,respectively.The mice were exposed to nano-TiO₂ via oral gavaging for 30 days.The semen quality of mice was estimated.The method of HE staining was used to observe histopathological changes of the testis.Commercial kits were applied to detect the SOD activity,MDA content,POD activity and scavenging superoxide anion activity.2.The mRNA sequencing technology was applied to study the genes changes between 50 mg/kg BW TiO₂ treatment group and control group,the differentially expressed genes were screened,and the data was analyzed by bioinformatics tools.Results:1.After the treatment of nano-TiO₂,the mouse sperm vitality decreased,the sperm deformity rate and testicular cells micronucleus rate increased,and the indexes have a dose dependent effect.The testicular sections of 100 mg/kg BW nano-TiO₂ treatment group showed that spermatogenic cells arranged in disorder,bureaucratic vacuolization,tubule diameter increased,the tube wall became thinning,spermatogenic cell layer reduced.Compared with that of the control group,SOD activity of 100mg/kg BW nano-TiO₂ treatment group decreased significantly?P<0.05?;MDA content and POD activity in 50 and 100mg/kg BW nano-TiO₂ treatment group was significantly higher than that of the control group?P<0.05?;The Scavenging superoxide anion activity in 100mg/kg BW nano-TiO₂ treatment group were significantly higher than as compared to the control?P<0.05?.2.The result showed that 568 genes were significantly altered in testis from mice treated by nano-TiO₂compared to the control group.Those altered genes related to immune system process,RNA splicing,mRNA processing,spermatogenesis and so on.There were some signaling pathways such as PI3K-Akt pathway,FAK pathway,Hippo pathway,Chemokine pathway,which may take part in the male reproductive toxicity induced by nano-TiO₂.Conclusions:Nano-TiO₂ has male reproductive toxicity,and can induce the decrease of semen quality and histopathological changes of testicular tissue.The mechanism of the male reproductive toxicity was perhaps associated with the oxidative damage and genes expression change in testicular tissue induced by nano-TiO₂.