中国现代医学杂志2018,Vol.28Issue(9):13-21,9.DOI:10.3969/j.issn.1005-8982.2018.09.003
母鼠长期低剂量锰染毒对子代大鼠睾丸氧化应激状态及生精细胞凋亡的影响
Effect of maternal chronic exposure of low-dose manganese on spermatogenic cells of offspring rats
摘要
Abstract
Objective To investigate the effect of chronic exposure of low-dose manganese chloride on spermatogenic cells of offspring rats. Methods Totally 32 healthy female SD rats were randomly divided into control group, low dose group, middle dose group and high dose group (n = 8). Rats in manganese exposure group received different doses of manganese chloride (2, 4, and 8 mg/kg in low dose group, middle dose group and high dose group, respectively) once a day, 5 days a week in a total of 8 weeks. Rats in control group were treated with saline for 8 weeks. After mating with normal male SD rats, female rats were continuously exposed to manganese during pregnancy and lactation as mentioned above. Testes of 12 week old offspring were harvested. HE staining was performed to observe the structure of seminiferous tubules. The expression levels of Fox03a, Bim, Caspase-9 mRNA, and protein in testis were identified by real-time PCR, immunohistochemistry, and Western blotting. Apoptosis rate of spermatogenic cells was detected by TUNEL. Results Morphological changes of seminiferous tubules in manganese exposure groups were observed including decrease of spermatogenic cell, disorder of spermatogenic cell structure and reduction of mature sperms. Abnormality was more severe along with increase of manganese exposure. Density and activity of sperms decreased while deformity ratio increased significantly in middle and high dose groups when compared with control group (P < 0.05). Activity of SOD, CAT and GSH-Px in the testis of rats exposed to manganese decreased dramatically while levels of MDA and ROS increased in dose dependent manner when compared with control group (P < 0.05). The expression levels of Fox03a, Bim and Caspase-9 increased in dose dependent manner when compared with control group (P < 0.05). Apoptosis of spermatogenic cells in manganese exposed groups were significantly enhanced in dose dependent manner compared with control group (P < 0.01). Conclusion Chronic maternal exposure of manganese leads to apoptosis of spermatogenic cells in offspring rats through activating oxidation mediated Caspase-9 signaling pathway.关键词
锰/抗氧化酶/叉头蛋白转录因子O 3a/细胞死亡调节子/凋亡Key words
manganese/FOXO3a/Bim/apoptosis分类
医药卫生引用本文复制引用
王乾兴,于明明,张先平..母鼠长期低剂量锰染毒对子代大鼠睾丸氧化应激状态及生精细胞凋亡的影响[J].中国现代医学杂志,2018,28(9):13-21,9.基金项目
贵州省自然科学基金(No:黔科合J字[2011]2282 ) (No:黔科合J字[2011]2282 )