邻苯二甲酸二(2-乙基)己酯诱导小鼠尿道下裂及对阴茎TGF-β1表达的影响

目的 用邻苯二甲酸二(2-乙基)己酯(DEHP)诱导建立先天性尿道下裂小鼠模型,研究DEHP对胎鼠阴茎内转化生长因子β1(TGF-β1)表达的影响.探讨尿道下裂发生机制.方法 C57BL/6孕鼠随机分为4组:玉米油对照组、DEHP低、中、高剂量组(i00、200、500 nag·kg-1·d-1).各组分别于母鼠孕期12d至17d(GD12～17)持续经口灌注给药.测量GD19雄性胎鼠体重、肛门至尿道口距离(AGD),通过尿道管型(UC)检测尿道解剖组织结构,比较尿道发育情况.应用免疫印迹(Western blot)检测胎鼠阴茎内TGF-β1蛋白量的表达水平.结果 DEHP成功诱导出尿道下裂小鼠动物模型,中、高剂量组AGD及前尿道较对照组明显缩短(P<0.001).实验组阴茎内TGF-β1蛋白表达水平随DEHP剂量增加而逐渐上升.结论 DEHP成功诱导建立先天性尿道下裂小鼠模型,胎鼠阴茎内TGF-β1蛋白异常表达可能是尿道下裂的发生机制之一.

Di(2-ethylhexyl) phthalate induces hypospadic in mice and its effect on the expression of TGF-β1 in genital tubercles

Objective To induce hypospadias in mice with di(2-ethylhexyl)phthalate (DEHP), and investigate the expression of TGF-β1 in fetal mice genital tubercles. Methods Pregnant C57BL/6 mice were randomly divided into 4 groups: control and DEHP (100,200, 500 mg·kg-1· d-1) groups. Mice were garaged from gestation day 12 to 17 (GD12～17). Fetal mice were harvested at GD19. We established urethral casts (UC) to compare urethral development, following the analyzed body weight and anogenital distance (AGD). The level of TGF-β1 protein was investigated by western blot. Results Hypospadias was induced in fetal male mice. The AGD and anterior urethra length in DEHP 200 mg·kg-1. d-1 and 500 mg·kg-1·d-1 groups were significantly shorter than those of control group (P<0.001). The levels of TGF-β1 protein were upregulated in experimental groups and positively related with the dose of DE-HP. Conclusions Murine model of hypospadias has been established successfully by treatment with DEHP, and up-regulated TGF-β1 protein may be one of the pathogenesis of hypospadias.