Hippo信号通路在乙烯菌核利致小鼠尿道下裂中的作用  

Role of Hippo signaling pathway in mice hypospadias induced by vinclozolin

作　　者：杨谨如 尹洪萍[2] 张玉静 阎政礼[1] 付虎[1] 朱勇飞[1] Yang Jinru;Yin Hongping;Zhang Yujing;Yan Zhengli;Fu Hu;Zhu Yongfei(Department of Preventive Medicine,Medical School,Hunan Normal University,Changsha 410013,China;School of Medicine,Hangzhou Normal University,Hangzhou 310018,China)

机构地区：[1]湖南师范大学医学院预防医学系,长沙410013 [2]杭州师范大学医学院,杭州310018

出　　处：《卫生研究》2019年第4期615-620,共6页Journal of Hygiene Research

基　　金：湖南省自然科学基金(No.2019JJ40194)

摘　　要：目的观察Hippo信号通路在乙烯菌核利致小鼠尿道下裂中的作用。方法将8周龄ICR孕鼠随机分为实验组和对照组,每组各10只,实验组在孕12~18 d连续7天经口给予400 mg/(kg·d)乙烯菌核利,对照组给予等体积的大豆油。分别于子鼠出生后第60天随机取实验组和对照组小鼠阴茎各20条,采用实时荧光定量PCR检测Hippo信号通路的关键基因Mst1、Lats1、Taz、Yap及雄激素受体基因Ar的表达丰度,Western blot方法检测Hippo信号通路下游Yes相关蛋白(Yap)的表达及其磷酸化水平。结果与对照组雄性子鼠相比,实验组雄性子鼠的肛门生殖器距离明显缩短[(9.2501±2.5504)vs.(16.1253±1.3562) mm,P<0.05]、阴茎质量明显较轻[(0.0293±0.0075)vs.(0.4731±0.004) g,P<0.05]、阴茎长度缩短[(5.3875±0.4524)vs.(12.4688±1.2290) mm,P<0.05],阴茎直径也较对照组小鼠小[(1.5513±0.1158)vs.(2.6013±0.1469) mm,P<0.05]。对照组小鼠阴茎中Hippo信号通路的关键基因Mst1、Lats1、Taz、Yap及雄激素受体基因Ar均表达;实验组Yap、Ar未表达,Mst1、Lats1的表达丰度高于对照组(6.6097±1.3188 vs. 0.3517±0.1524, 5.7071±2.7210 vs. 0.1235±0.0658,P<0.05),Taz的表达丰度低于对照组(0.3937±0.1519 vs. 3.2329±0.4339,P<0.05)。实验组小鼠阴茎Yap表达量降低(0.3348±0.0639 vs. 0.8023±0.4275,P<0.05)、磷酸化程度高于对照组(3.9940±0.2177 vs. 0.3128±0.0867,P<0.05)。结论乙烯菌核利致小鼠尿道下裂模型中,Ar未表达,Hippo信号通路被激活,Yap磷酸化增加,该通路可能在乙烯菌核利致雄性小鼠尿道下裂中起重要作用。OBJECTIVE To observe the role of Hippo signaling pathway in mice hypospadias induced by vinclozolin. METHODS After 8 weeks of ICR mice were conceived, they were divided randomly into the treatment and the control groups(10 for each group). Vinclozolin was orally administraed to the pregnant mice in the treatment group with 400 mg/(kg·d) during gestation days 12-18, while those of the control group were treated with equal volume of soybean oil. About 60 days after birth, 20 penises of the mouse offspring were taken randomly from both of the two groups separately. And furthermore, the relative expression abundance of Hippo signaling pathway key genes(Mst1,Lats1,Taz,Yap),androgen receptor gene Ar of all the samples were measured by the real-time quantity reverse transcript polymerase chain reaction(qPCR). The Yes-related protein(Yap) and its phosphorylation in the downstream of Hippo signaling pathway were measured by Western blot. RESULTS Compared with the male mice of the control group, the anal genital distances of the treatment group were significantly shortened((9.2501±2.5504) vs.(16.1253±1.3562) mm, P<0.05), the quality of the penises was significantly less than((0.0293±0.0075) vs.(0.4731±0.004) g, P<0.05), the length of the penises was shorter((5.3875±0.4524) vs.(12.4688±1.2290) mm, P<0.05), and the diameters of the penises were also less than the control((1.5513±0.1158) vs.(2.6013±0.1469) mm, P<0.05). All the genes in the penises of the control group were expressed. The Yap and Ar in the treatment group’s penises were not expressed, the expression abundance of Mst1 and Lats1 was higher than that of the control(6.6097±1.3188 vs. 0.3517±0.1524,5.7071±2.7210 vs. 0.1235±0.0658, P<0.05), and the expression abundance of Taz was lower than that of the control(0.3937±0.1519 vs. 3.2329±0.4339, P<0.05). The expression of Yap was decreased in the treatment group(0.3348±0.0639 vs. 0.8023±0.4275, P<0.05), and the phosphorylation level of Yap was higher than that of the control group(3.9940±0.2177 vs.

关 键 词：乙烯菌核利 尿道下裂 Hippo信号通路 雄激素受体基因 Yes相关蛋白 

分 类 号：Q132.7[生物学—普通生物学] S482.22[农业科学—农药学]