Murdoch Children's Research Institute, Melbourne, Australia.
J Pediatr Surg. 2011 Dec;46(12):2363-9. doi: 10.1016/j.jpedsurg.2011.09.032.
BACKGROUND/AIMS: How androgens control inguinoscrotal descent remains controversial but may include canonical Wnt signaling via the transcriptional co-activator β-catenin. The canonical Wnt pathway transcribes genes regulating mesenchymal cell migration, fate, extracellular matrix remodeling, and in addition Axin2, a feedback product that reliably identifies Wnt activation. The relationship between β-catenin and androgen receptor warranted investigation into the involvement of the canonical Wnt pathway in testicular descent.
Gubernacula from male Sprague-Dawley control (n = 22) and flutamide-treated (n = 18) rats at E17, E19, and D0 time-points were processed for immunohistochemistry. Sagittal sections stained for presence of androgen receptor, Axin2, and β-catenin were analyzed by fluorescent confocal microscopy.
At E19, β-catenin was strongly expressed in the membrane of developing cremaster muscle cells and the cytoplasm of gubernacular core cells. Axin2 expression was ubiquitous in nuclei of gubernacular mesenchymal cells, representing canonical Wnt signaling. After androgen blockade, Axin2 was conspicuously absent in the fibroblasts of the gubernacular core while remaining unaffected elsewhere. Reduced staining of Axin2 in E17 and D0 gubernacula suggests that Wnt signaling coincides with androgen programming.
Axin2 expression in the E19 gubernaculum confirms canonical Wnt pathway activation. Its absence in the core of flutamide-treated gubernacula indicates Wnt down-regulation. As androgen is required for inguinoscrotal descent, downstream Wnt signaling may control initial gubernacular remodeling. Defects in this complex molecular process may play a role in cryptorchidism.
背景/目的：雄激素如何控制腹股沟阴囊下降仍存在争议，但可能包括通过转录共激活因子β-连环蛋白的经典 Wnt 信号通路。经典 Wnt 途径转录调节间充质细胞迁移、命运、细胞外基质重塑的基因，此外还有 Axin2，它是可靠地识别 Wnt 激活的反馈产物。β-连环蛋白和雄激素受体之间的关系需要研究经典 Wnt 途径在睾丸下降中的参与。
E17、E19 和 D0 时间点的雄性 Sprague-Dawley 对照（n = 22）和氟他胺处理（n = 18）大鼠的生殖褶进行免疫组织化学处理。对存在雄激素受体、Axin2 和 β-连环蛋白的矢状切片进行荧光共聚焦显微镜分析。
在 E19 时，β-连环蛋白在发育中的提睾肌细胞膜和生殖褶核心细胞的细胞质中强烈表达。Axin2 表达在生殖褶间充质细胞的核中普遍存在，代表经典 Wnt 信号通路。雄激素阻断后，Axin2 在生殖褶核心的成纤维细胞中明显缺失，而其他部位不受影响。E17 和 D0 生殖褶中 Axin2 染色减少表明 Wnt 信号与雄激素编程一致。
E19 生殖褶中 Axin2 的表达证实了经典 Wnt 途径的激活。氟他胺处理生殖褶核心中 Axin2 的缺失表明 Wnt 下调。由于雄激素是腹股沟阴囊下降所必需的，下游 Wnt 信号可能控制初始生殖褶重塑。这个复杂的分子过程中的缺陷可能在隐睾症中起作用。
