Loebenstein Moshe, Hutson John, Li Ruili
FD Stephens Surgical Research Group, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
FD Stephens Surgical Research Group, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia; Department of Urology, Royal Children's Hospital, Parkville, Victoria, 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia.
J Pediatr Surg. 2018 Sep;53(9):1770-1775. doi: 10.1016/j.jpedsurg.2017.12.026. Epub 2018 Jan 31.
In congenital undescended testis (UDT) in humans, thermal insult damages early germ cell development during mini-puberty (3-6months) causing increased risk of both cancer and infertility. In rodents however, UDT causes infertility but not cancer. In the TS rat with congenital UDT we hypothesized that early germ cell development would be normal as UDT only becomes manifest at 3-4weeks (and the germ cells only become sensitive to thermal injury) after minipuberty is complete at 1week.
Normal testis and potential UDT from unilateral cryptorchid TS rats were collected at week 1 and 4 and processed into paraffin sections labeled for Sertoli cells (AMH), early germ cells (MVH) and spermatogonial stem cells (PLZF). Confocal microscopic images and Fiji Image J were used to count cells in testicular tubules with paired T-test statistical analysis.
Total germ cells/tubule, basement membrane-bound germ cells/tubule, and Sertoli cells/tubule were unchanged between normally descending and future UDT at 1-4weeks old (P>0.05) Total germ cells/tubule and spermatogonial stem cells/tubule increased dramatically between weeks 1 and 4.
Rat gonocyte transformation is normal in both normally descending and future UDT. This suggests that congenitally cryptorchid rats may not develop testicular cancer because gonocytes (the putative origin of malignant degeneration) normally transform into spermatogonial stem cells before UDT occurs and the risk of thermal injury develops. This suggests the TS rat may be a good model for acquired UDT in human where the abnormal testicular position develops after gonocyte transformation is completed in the first year.
在人类先天性隐睾症（UDT）中，热损伤会在小青春期（3 - 6个月）期间损害早期生殖细胞发育，从而增加癌症和不育的风险。然而，在啮齿动物中，UDT会导致不育但不会引发癌症。在患有先天性UDT的TS大鼠中，我们推测早期生殖细胞发育将是正常的，因为UDT仅在1周龄小青春期结束后3 - 4周（此时生殖细胞才开始对热损伤敏感）才会显现。
在第1周和第4周收集单侧隐睾TS大鼠的正常睾丸和潜在UDT，并将其处理成石蜡切片，用抗苗勒管激素（AMH）标记支持细胞、用MVH标记早期生殖细胞、用PLZF标记精原干细胞。使用共聚焦显微镜图像和Fiji Image J对睾丸小管中的细胞进行计数，并采用配对t检验进行统计分析。
在1 - 4周龄时，正常下降的睾丸和未来的UDT之间，每小管的总生殖细胞数、基底膜结合的生殖细胞数和支持细胞数均无变化（P>0.05）。每小管的总生殖细胞数和精原干细胞数在第1周和第4周之间显著增加。
在正常下降的睾丸和未来的UDT中，大鼠生殖母细胞的转化都是正常的。这表明先天性隐睾大鼠可能不会发生睾丸癌，因为生殖母细胞（恶性变性的假定起源）在UDT发生和热损伤风险出现之前通常会正常转化为精原干细胞。这表明TS大鼠可能是人类后天性UDT的良好模型，在人类中，异常的睾丸位置是在第一年生殖母细胞转化完成后才出现的。
