Gonocyte transformation in a congenitally cryptorchid rat is normal and may be similar to the situation reported in human acquired cryptorchidism

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Cryptorchidism; Germ cells; Gonocytes; Heat; Testis.