中文摘要：

目的：雌激素与尿道下裂的发生关系密切,本研究旨在比较尿道下裂患儿包皮和同龄正常儿童包皮中转录激活因子3（ATF3）和结缔组织生长因子（CTGF）的表达,明确二者与尿道下裂的关系,探寻雌激素引起尿道下裂的分子机制。方法：从包皮中分离成纤维细胞并原代培养,用不同浓度（1.0μmol/L、0.1μmol/L、10.0nmol/L、1.0nmol/L、0.1nmol/L）的17-β乙炔雌二醇（17-EE）处理2h,或选择0.1μmol/L的17-EE处理不同时间（0.5、1、2、4、8、16、24h）,观察17-EE对ATF3和CTGF表达的影响。MTT法检测17-EE对细胞增殖的影响,RT-PCR法观察成纤维细胞ATF3和CTGF表达情况。结果：尿道下裂患者包皮中ATF3和CTGF的表达显著高于正常人包皮组织（P〈0.05）;高浓度的17-EE干预对包皮成纤维细胞有抑制作用;在17-EE干预早期（1～2h）ATF3的表达呈现一过性增加;CTGF的表达在24h内17-EE干预未见明显变化。结论：ATF3和CTGF是与尿道下裂密切相关基因,雌激素可能通过上调ATF3和CTGF的表达参与调节生殖结节的异常发育,导致尿道下裂。

英文摘要：

Objective： Estrogen is closely associated with hypospadias. The present study was to explore the molecular mechanism of hypospadias caused by estradiol. Methods ： Fibroblasts obtained from the prepuce of hypospadiac and normal children were cultured in vitro and treated with 17-13 ethinyl estradiol （ 17-EE ） at the concentrations of 1 μmol/L to 0. 1 nmol/L for 2 hours, or at 0.1 μmol/L for 0.5, l, 2, 4, 8, 16 and 24 hours. MTT assay was used to evaluate the effect of 17-EE on the proliferation of the ceils, and RT-PCR was employed to detect the expressions of the activating transcription factor-3 （ ATF3 ） and connective tissue growth factor （CTGF） in the hypospadiac tissue. The results were compared with those obtained from the nonhypospadiac tissue. Results： The expressions of ATF3 and CTGF were significantly upregnlated in the hypospadiac tissue as compared with the nonhypospadiac group. At the concentration of 1 μmol/L, 17-EE significantly inhibited the proliferation of the cells. ATF3 mRNA was elevated at 1 - 2 hours, while CTGF mRNA showed no significant changes in 24 hours. Conclusion： ATF3 and CTGF are two candidate genes involved in the etiology of hypospadias. And estradiol may induce hypospadias by upregulating the expressions of ATF3 and CTGF.