Ren Xiantian, Mi Jie, Jia Huimin, Gao Hong, Bai Yuzuo, Wang Weilin
Department of Pediatric Surgery, Shengjing Hospital, China Medical University, PR China.
Department of Pediatric Surgery, Shengjing Hospital, China Medical University, PR China.
Exp Mol Pathol. 2015 Aug;99(1):81-5. doi: 10.1016/j.yexmp.2015.05.008. Epub 2015 May 27.
Embryogenesis is orchestrated by the wingless-type MMTV integration site family (WNT) signaling pathways, including Wnt3a. This study was performed to investigate the expression of Wnt3a in the terminal hindgut in ethylenethiourea (ETU)-exposed rat embryos with anorectal malformations (ARMs) and its potential association between Wnt3a and the maldevelopment of the terminal hindgut in ARMs. ARM rat embryos were induced by ethylenethiourea on embryonic day 10 (E10). The expression levels of protein and mRNA of Wnt3a were confirmed using immunohistochemistry staining, Western blotting analyses, and quantitative real-time PCR (qRT-PCR) in normal rat and ARM embryos. Immunostaining revealed a variation in the expression of Wnt3a in the developing terminal hindgut of ARM embryos. The expression of Wnt3a in the terminal hindgut of ARM rat embryos decreased at both the mRNA level and protein level (P<0.05) compared with normal tissues. This study demonstrated that the expression of Wnt3a in the ARMs of ETU-exposed rat embryos was remarkably reduced, which indicated its potential role in the pathogenesis of the terminal hindgut maldevelopment in ARMs.
胚胎发育由无翅型MMTV整合位点家族(WNT)信号通路调控,包括Wnt3a。本研究旨在调查Wnt3a在乙硫脲(ETU)暴露致肛门直肠畸形(ARM)的大鼠胚胎终末后肠中的表达情况,以及Wnt3a与ARM终末后肠发育异常之间的潜在关联。在胚胎第10天(E10)用乙硫脲诱导产生ARM大鼠胚胎。采用免疫组织化学染色、蛋白质印迹分析和定量实时PCR(qRT-PCR)检测正常大鼠和ARM胚胎中Wnt3a的蛋白质和mRNA表达水平。免疫染色显示ARM胚胎发育中的终末后肠Wnt3a表达存在差异。与正常组织相比,ARM大鼠胚胎终末后肠中Wnt3a在mRNA水平和蛋白质水平均降低(P<0.05)。本研究表明,ETU暴露的大鼠胚胎ARM中Wnt3a的表达显著降低,这表明其在ARM终末后肠发育异常发病机制中的潜在作用。