TGF-β1、TGF-βrⅢ在邻苯二甲酸二丁酯诱导尿道下裂新生雄性仔鼠生殖结节中的表达及意义  

The abnormal expression of TGF-β1、TGF-βrⅢ in genital tubercle of newborn hypospadiac male rats induced by maternal exposure to Di-n-butyl phthalate

作　　者：朱英坚[1] 蒋君涛[1] 马隆[2] 张捷[1] 洪艳[1] 廖凯[3] 刘国华[1] 

机构地区：[1]上海交通大学附属第一人民医院泌尿外科,200080 [2]江苏省中医院泌尿外科 [3]南京医科大学第一临床医学院

出　　处：《中华小儿外科杂志》2009年第11期789-792,共4页Chinese Journal of Pediatric Surgery

基　　金：上海市科委基础重点研究项目（编号：07JC14030）和上海市科委自然基金（编号：08ZR1411700）资助

摘　　要：目的通过验证大鼠孕期污染邻苯二甲酸二丁酯（DBP）所致尿道下裂雄性仔鼠生殖结节中TGF-β1、TGF-βrⅢ的表达异常，探讨其在DBP生殖毒性过程中的作用机制。方法孕鼠20只，随机分二组，在怀孕（GD）14～18d期间，每天分别灌胃给予大豆油、DBP750mg／kg，出生第一天（PNDI），统计仔鼠出生数，尿道下裂发生率。PND7，雄性仔鼠称重，测量雄性仔鼠肛门至生殖器距离（AGD），拍摄尿道下裂大体图片，取尿道下裂生殖结节进行病理学切片检查，用实时定量逆转录聚合酶链反应（Real-time quantitativePCR）方法检测生殖结节中的TGF-β1、TGF-βrⅢ的mRNA表达水平。结果DBP染毒后导致新生仔鼠与正常组相比数量明显减少，雄性仔鼠尿道下裂的发生率为：43．75％。PND7时，雄性仔鼠体重明显下降，AGD明显缩短。大体图片和病理切片显示典型尿道下裂改变。同时与对照组相比，DBP导致尿道下裂雄性仔鼠生殖结节中TGF-β1、TGF-βrⅢ的mRNA表达水平明显下降。结论DBP对母体有着明显的毒性作用，DBP干预了TGF-β1、TGF-βrⅢ基因的表达，导致子代的生殖结节发育异常，引起尿道下裂。Objective To evaluate the expression of TGF-β1 and TGF-β rⅢ in genital tubercle （GT） of hypospadiac male rats induced by maternal exposure to DBP. Methods Twenty timed pregnant rats were randomly divided into 2 groups and were given Di-n-butylphthalate （DBP） by gastric in- tubation at a dose of 0 or 750 mg/kg from gestation day（GD） 14 to GD18. On postnatal day （PND 1）, live pups were counted and male pups were examined for hypospadias. On PNDT, The anogenital distance （AGD） and body weight of male pups were measured. The gross image and the histologic changes of hypospadiac genitalia were checked. Meanwhile, real-time quantitative PCR were used to quantify mRNA expression of TGF-β1 and TGF-β rⅢ in GT of hypospadiac male rats. Results The number of live pups in the DBP treating group was significantly decreased and the incidence of hypospadias was 43. 75%. The body weight and the AGD of hypospadiac male rats were significantly decreased on PND7. The general and the pathological changes of hypospadiac genitalia were also observed. Moreover,significantly decreased gene expressions of TGF-β1 and TGF-β rⅢ were found. Conclusions There were obviously toxic effects of DBP to the pregnant rats. The down-regulation expression of TGF-β signaling molecules might lead to the development of hypospadias induced by maternal exposure to DBP.

关 键 词：邻苯二甲酸二丁酯 尿道下裂 转化生长因子Β1 转化生长因子Β rⅢ 

分 类 号：R686[医药卫生—骨科学]