Douglas Stephens Surgical Research Laboratory, Murdoch Children's Research Institute, Melbourne, Australia.
J Pediatr Surg. 2013 Jul;48(7):1573-7. doi: 10.1016/j.jpedsurg.2012.08.038.
BACKGROUND/AIMS: Robinow syndrome is caused by mutations in Wnt-5a or its receptor Ror2 and can lead to cryptorchidism, though the mechanisms are unclear. Wnt-5a knock-out mice fail to undergo gubernacular swelling, similar to insulin-like hormone 3 (INSl-3) knock-out mice. We aimed to characterise Wnt-5a and Ror2 expression in rat gubernacula to better understand how Wnt-5a signalling affects testicular descent.
Sprague-Dawley rats (n = 27) were collected with ethics approval (A644) at embryonic days (E) 15, 17, 19 and postnatal day (D) 2. Control and antiandrogen-treated groups were processed for immunohistochemistry for Wnt-5a, Ror2 and β-catenin. Sagittal sections were examined using confocal microscopy.
Wnt-5a and Ror2 were strongly expressed in the gubernacular bulb at E17 controls, their levels declining at E19 and almost absent by D2. Wnt-5a significantly co-localised with the important transcription factor β-catenin at E17. There was no obvious difference in staining with androgen blockade.
Wnt-5a, through Ror2 and β-catenin may play a vital role in regulating the gubernacular swelling reaction downstream of INSL-3. Human mutations in Wnt-5a or Ror2 could prevent early gubernacular growth, as suggested by undescended testes in 70% of patients with Robinow Syndrome.
背景/目的：Robinow 综合征是由 Wnt-5a 或其受体 Ror2 的突变引起的，可导致隐睾，但机制尚不清楚。Wnt-5a 敲除小鼠未能经历引带肿胀，类似于胰岛素样激素 3 (INSl-3) 敲除小鼠。我们旨在描述 Wnt-5a 和 Ror2 在大鼠引带中的表达，以更好地了解 Wnt-5a 信号如何影响睾丸下降。
使用伦理批准（A644）在胚胎第 15、17、19 天（E）和出生后第 2 天（D）收集 Sprague-Dawley 大鼠（n = 27）。对照组和雄激素拮抗剂处理组进行 Wnt-5a、Ror2 和 β-连环蛋白的免疫组织化学处理。使用共聚焦显微镜检查矢状切片。
Wnt-5a 和 Ror2 在 E17 对照组的引带球部强烈表达，其水平在 E19 时下降，在 D2 时几乎不存在。Wnt-5a 在 E17 时与重要转录因子β-连环蛋白明显共定位。雄激素阻断无明显差异。
Wnt-5a 通过 Ror2 和 β-连环蛋白可能在调节 INSL-3 下游的引带肿胀反应中发挥重要作用。Wnt-5a 或 Ror2 中的人类突变可能会阻止早期引带生长，如 70%的 Robinow 综合征患者未下降的睾丸所表明的那样。
