Fas/FasL系统在邻苯二甲酸二丁酯睾丸毒性机制中的作用

The role of Fas/FasL system in the male reproductive toxicity of di-n-butyl phthalate in rats

目的探讨细胞凋亡Fas/FasL系统在邻苯二甲酸二丁酯(DBP)的雄性生殖毒性机制中的作用。方法在大鼠多代繁殖实验的基础上,运用免疫组织化学染色的方法,通过对睾丸组织损伤的观察和细胞凋亡相关蛋白(Fas/FasL)的检测和分析,探讨不同剂量DBP对成年F1代大鼠(PND70天)睾丸损害的情况及可能的作用机制。结果与对照组相比较,随着DBP染毒剂量的增高,PND70天F1代雄性大鼠睾丸曲细精管生精上皮退化变性,生精细胞脱落至曲细精管管腔面,甚至有部分曲细精管内的生精细胞耗竭;免疫组织化学染色结果表明,与对照组相比,中、高剂量组(每天250和500mg/kg)大鼠睾丸组织Fas/FasL染色范围扩大,着色细胞数量增多,且存在剂量-反应关系。结论DBP对大鼠睾丸生精细胞损伤可能是由于DBP启动了睾丸支持细胞Fas/FasL系统,阻抑生精过程造成的,Fas/FasL系统在DBP的雄性生殖毒性中起一定作用。

Purpose To figure out the role of the Fas/FasL system in the male reproductive toxicity of di-n-butyl phthalate（DBP） in rats. Methods Based on the multiple-generation reproductive and developmental test, the damage of DBP on rats＇ testis and Fas/FasL expression of testis were observed by the method of histopathological and immunohistochemical staining. Results Compared with the control group, severe damages of the reproductive system of F1 male rats （testicular atrophy, degeneration or exfoliation of the germinal epithelium, depletion of germ cells, etc. ） could still be observed in the groups of 250 and 500 mg/kg per day. Meanwhile, the staining range of the rat testis （PND 70 d group） in DBP-treated groups expanded obviously and more stained cells in these groups were found. These results showed that DBP exposure caused testes lesions in a dose-dependent manner and the damage of DBP on rats＇ testis was paralleled with Fas/FasL expression. Conclusions DBP could destroy the tight junction between sertoli cells and then induce the detachment of germ cells from germ epithelium by activating the Fas/FasL system. This might be one of the reseaons of testis atropy, which was observerd in phthalate-treated rats.