Zhou Yao-Jun, Wei Jun-Feng, Zhang Li-Feng, Wang Yong, Zhang Wei
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Zhonghua Nan Ke Xue. 2012 Mar;18(3):222-6.
To detect the differential expression of Notch1 in the genital tubercle (GT) of fetal male rats with hypospadias induced by maternal exposure to Di-n-butyl phthalate (DBP) and that in normal control fetal rats in order to further explore the role of Notch1 in DBP-induced hypospadias.
Twenty pregnant SD rats were equally and randomly divided into an experimental and a control group, the former given DBP and the latter soybean oil intragastrically at 800 mg/(kg x d) and 2 ml/d respectively from gestation day (GD) 14 to GD 18. On GD 19, the birth weight (BW), anogenital distance (AGD) and hypospadias incidence were recorded, GTs of the fetal male rats collected, and the expression of Notch1 analyzed by Western blot and immunohistochemistry.
The BW of the fetal male rats was (4.40 +/- 0.30) g in the experimental group, significantly lower than (6.11 +/- 0.40) g in the control (P <0.05), and the AGD was (2.17 +/- 0.18) mm in the former, markedly shorter than (3.28 +/- 0.16) mm in the latter (P<0.05). The incidence of hypospadias was 42.9%. The relative expression of Notch1 was remarkably lower in the hypospadiac rats than in the normal controls (0.671 +/- 0.021 vs 1.327 +/- 0.031, P<0.05), and it was mainly located in the epithelial cells of the GT. The staining intensity was obviously weaker in the hypospadias than in the normal control group.
DBP has an obvious toxic effect on fetal male rats and can change the expression of Notch1 in the GT. It possibly affects cell proliferation and apoptosis and epithelial-to-mesenchymal transition (EMT), resulting in the occurrence of hypospadias.
检测孕期暴露于邻苯二甲酸二丁酯（DBP）所致尿道下裂雄性胎鼠生殖结节（GT）中Notch1的差异表达，并与正常对照胎鼠进行比较，以进一步探讨Notch1在DBP诱导尿道下裂中的作用。
将20只孕SD大鼠平均随机分为实验组和对照组，从妊娠第14天（GD 14）至GD 18，前者每天按800 mg/（kg·d）给予DBP灌胃，后者每天按2 ml/d给予大豆油灌胃。在GD 19时，记录出生体重（BW）、肛门生殖距离（AGD）和尿道下裂发生率，收集雄性胎鼠的GT，采用蛋白质免疫印迹法和免疫组织化学法分析Notch1的表达。
实验组雄性胎鼠BW为（4.40±0.30）g，显著低于对照组的（6.11±0.40）g（P<0.05）；实验组AGD为（2.17±0.18）mm，明显短于对照组的（3.28±0.16）mm（P<0.05）。尿道下裂发生率为42.9%。尿道下裂大鼠中Notch1的相对表达明显低于正常对照组（0.671±0.021 vs 1.327±0.031，P<0.05），且主要位于GT的上皮细胞中。尿道下裂组的染色强度明显弱于正常对照组。
DBP对雄性胎鼠有明显毒性作用，可改变GT中Notch1的表达。它可能影响细胞增殖、凋亡及上皮-间质转化（EMT），导致尿道下裂的发生。
