Effects of chronic low-dose manganese exposure on cell cycle arrest and apoptosis in spermatogenic cells of rat offspring / 实用医学杂志

ABSTRACT

Objective To investigate the effect of chronic low-dose manganese chloride exposure on cell cycle and apoptosis of spermatogenic cells in offspring rat. Methods 32 healthy female SD rats were randomly divided into control and manganese exposure groups(n=8).The manganese exposure group respectively received 2,4 and 8 mg/Kg MnCl2·4H2O,while the control group was treated with equal volume saline for 8 weeks(1 time/d,5 d/w).After mating with normal male SD rats and determining conception,female rats were continued to be ex-posed to manganese during pregnancy and lactation. There were. 8 offspring male rats in each group. In the 12th week,the offspring rates were randomly executed and their testes were used to observe the structure of seminifer-ous tubules by HE staining. The expression of FOXO3A,cell cycle associated proteins P16,P21,CDK2, CDK4,CDK6 and apoptosis related proteins BIM,Caspase-9 in the testis of offspring male rats were detected by western blotting. In addition,the apoptosis of spermatogenic cells was detected by TUNEL. Results(1)With the increase of administered-MnCl2 dosage,the seminiferous tubule showed various changes,including layers of spermatogenic cell decreased,spermatogenic cells arranged in disorder,the number of mature sperm in the lumen of seminiferous tubule significantly reduced.(2)The expression of FOXO3A,P16 and P21 increased while CDK2 and CDK4 decreased gradually with the increase manganese exposure dose. CDK6 expression was not significantly changed in all groups.(3)The expression of BIM,Caspase-9 and apoptotic index of spermatogen-ic cells increased gradually with the increase of manganese dose. Conclusion Chronic low-dose of manga-nese exposure could induce expression of FOXO3A,further cause cell cycle arrest and apoptosis of spermatogen-ic cells in offspring rat.