Wnt/β-catenin与NFκB信号通路在邻苯二甲酸二丁酯诱导雄性大鼠发生尿道下裂中的表达研究
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摘要
目的:利用邻苯二甲酸二丁酯(DBP)孕晚期暴露诱导子代SD大鼠发生尿道下裂,验证Wnt/β-catenin及NFκB信号通路中关键蛋白在胎鼠生殖结节中的差异表达,探讨该通路在DBP致大鼠生殖系统发育异常过程中的作用机制。
方法:孕SD大鼠20只,随机分为两组,在妊娠(GD)14～18天,每天分别通过灌胃给予DBP和大豆油800mg/kg,同时予GD19提取尿道下裂组与对照组胎鼠生殖结节组织,用Western blot检测β-连环蛋白(β-catenin),糖原合成酶-3β(GSK-3β)和NFκB的表达情况。用免疫组化验证Wnt通路重要调节因子GSK-3β的定位情况。
结果:DBP染毒后雄性胎鼠出生数量及体重较对照组明显下降,肛门生殖器距离(AGD)明显缩短,尿道下裂发生率为46.7%,同时尿道下裂组与对照组中β-catenin相对表达量的比值为0.505±0.014(n=10,P<0.05),GSK-3β与NFκB相对表达量的比值分别为1.903±0.018 (n=10,P<0.05)和3.661±0.021(n=10,P<0.05)。GSK-3β定位于尿道上皮细胞的胞质中。
结论:Wnt/β-catenin信号通路作为调节生长发育重要的因子之一,在DBP诱导的尿道下裂仔鼠及对照组中存在差异性表达,DBP可能通过干预这些调节胚胎发育相关信号通路的正常表达,从而引起GT生长发育发生异常,最终导致尿道下裂的发生。DBP导致雄性仔鼠阴茎组织中调节生殖发育相关通路表达异常,有助于深入探讨DBP影响雄性大鼠生殖系统发育及尿道下裂发生的作用机制,同时也为干预DBP的生殖发育毒性提供了重要信息。
Objective: To evaluate the expression of Wnt/β-catenin and NFκB pathway in hypopspadiac male rats treated by utero exposure to DBP.
Methods: Twenty pregnant rats were randomly divided into two groups and given DBP by gastric intubation at a dose of 0,800 mg/kg from gestation day(GD)14 to GD18.On GD19,Western blot analysis was used to quantify expression ofβ-catenin,GSK-3βand NFκB in GT of hypospadiac male rats.
Results: The body weight and the AGD of hypospadiac male rats significantly decreased. Moreover, the expression ofβ-catenin was significantly decreased and an increased expression of GSK-3βand NFκB in GT was observed(n=10,P<0.05). GSK-3βwas located in the urethral plate epithelium (UPE) by immunohistochemistry.
Conclusion: DBP could possibly affect the development of GT by regulating Wnt/β-catenin and NFκB pathway in fetal male rats. These results could provide us a possibility to interfere the reproductive toxicity of DBP by regulating specific pathway in GT tissues.
方法:孕SD大鼠20只,随机分为两组,在妊娠(GD)14～18天,每天分别通过灌胃给予DBP和大豆油800mg/kg,同时予GD19提取尿道下裂组与对照组胎鼠生殖结节组织,用Western blot检测β-连环蛋白(β-catenin),糖原合成酶-3β(GSK-3β)和NFκB的表达情况。用免疫组化验证Wnt通路重要调节因子GSK-3β的定位情况。
结果:DBP染毒后雄性胎鼠出生数量及体重较对照组明显下降,肛门生殖器距离(AGD)明显缩短,尿道下裂发生率为46.7%,同时尿道下裂组与对照组中β-catenin相对表达量的比值为0.505±0.014(n=10,P<0.05),GSK-3β与NFκB相对表达量的比值分别为1.903±0.018 (n=10,P<0.05)和3.661±0.021(n=10,P<0.05)。GSK-3β定位于尿道上皮细胞的胞质中。
结论:Wnt/β-catenin信号通路作为调节生长发育重要的因子之一,在DBP诱导的尿道下裂仔鼠及对照组中存在差异性表达,DBP可能通过干预这些调节胚胎发育相关信号通路的正常表达,从而引起GT生长发育发生异常,最终导致尿道下裂的发生。DBP导致雄性仔鼠阴茎组织中调节生殖发育相关通路表达异常,有助于深入探讨DBP影响雄性大鼠生殖系统发育及尿道下裂发生的作用机制,同时也为干预DBP的生殖发育毒性提供了重要信息。
Objective: To evaluate the expression of Wnt/β-catenin and NFκB pathway in hypopspadiac male rats treated by utero exposure to DBP.
Methods: Twenty pregnant rats were randomly divided into two groups and given DBP by gastric intubation at a dose of 0,800 mg/kg from gestation day(GD)14 to GD18.On GD19,Western blot analysis was used to quantify expression ofβ-catenin,GSK-3βand NFκB in GT of hypospadiac male rats.
Results: The body weight and the AGD of hypospadiac male rats significantly decreased. Moreover, the expression ofβ-catenin was significantly decreased and an increased expression of GSK-3βand NFκB in GT was observed(n=10,P<0.05). GSK-3βwas located in the urethral plate epithelium (UPE) by immunohistochemistry.
Conclusion: DBP could possibly affect the development of GT by regulating Wnt/β-catenin and NFκB pathway in fetal male rats. These results could provide us a possibility to interfere the reproductive toxicity of DBP by regulating specific pathway in GT tissues.
引文
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