摘要
目的利用糖皮质激素与邻苯二甲酸二丁酯（DBP）联合作用致大鼠尿道下裂，观察转录激活因子3（ATF3）在正常大鼠生殖结节（GT）与不同严重程度尿道下裂大鼠生殖结节中的差异表达，并探讨ATF3在尿道下裂发生中的作用机制。方法将sD孕鼠40只随机均分为4组，在妊娠14～18d（GD14～18）分别给予：A组：大豆油灌胃2ml／d；B组：地塞米松（DXM）O．1mg／（kg·d）皮下注射；c组：DBP700mg／（kg·d）灌胃；D组：DXM0．1mg／（kg·d）皮下注射加DBP700mg／（kg·d）灌胃。GDl9将各组孕鼠处死剖腹统计雄性仔鼠出生体质量（BW）及肛门生殖器间距离（AGD），取雄性仔鼠生殖结节，运用免疫印迹法和免疫组织化学方法分析ATF3的表达。结果DXM单独作用于孕鼠仅表现为仔鼠BW下降，但与DBP组合作用却能显著增强DBP的致畸作用，导致雄性仔鼠BW及AGD／BW明显减少。ATF3在A组的蛋白相对表达量为0．351±0．012，B组为0．336±0．015，C组为0．603±0．014，D组为0．851±0．016，C组或D组与A组，以及C组与D组之间的差异均有统计学意义（P〈0．05）；免疫组织化学结果显示ATF3主要定位于生殖结节的尿道上皮和侧翼间质，C组和D组免疫组织化学染色强度明显强于A组，而D组染色强于C组。结论DXM联合DBP进一步增强了DBP的致畸作用，提示尿道下裂的发生是环境中多因素协同作用的结果，ATF3在对照组与实验组生殖结节中的表达有明显变化，且随着尿道下裂程度的加重而表达增高，ATF3的高表达影响了生殖结节的发育及尿生殖褶的融合，这可能是尿道下裂发生的机制之一。
Objective To verify the differential expression of ATF3 in the genital tubercle (GT) of rats with hypospadias induced by maternal exposure to Di-n-butyl phthalate (DBP) or DBP + dexamethasone (DXM) in order to further explore the mechanism of hypospadias. Methods Forty pregnant SD rats were randomly divided into four groups which were given: group A, soybean oil oral gavage 2 ml/day;DBP (700 mg/kg gavage) + DXM (0. 1 mg/kg sc-injection) during gestational day (GD) 14-18. Pregnant rats were killed at GD 19, birth weight (BW) and anogenital distance (AGD) were recorded in the fetal rats, GT was harvested to verify the expression of ATF3 by Western blotting and immunohistochemistry. Results DXM alone had no effect except to reduce BW but could increase the teratogenic effect of DBP when combined with DBO. The BW and AGD/BW in group D were significantly lower than in group C. The expression of ATF3 had statisticall significant difference between groups C or D and group A, as well as between groups C and D (P ＜ 0. 05). ATF3 was mainly located in the urethral epithelium and mesenchyme. Conclusion These results suggests that exposure to common environmental chemicals in combination with environmental endocrine disrupters may increase the risk of male reproductive abnormalities,such as hypospadias. Up-regulation of ATF3 may affect urethral fold fusion, and then lead to the occurrence of hypospadias.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2011年第5期778-780,共3页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金资助项目（30872596）
