INVESTIGATIVE UROLOGY

Apoptosis and proliferation in human undescended testes
Ofordeme KG, Aslan AR, Nazir TM, Hayner-Buchan A, Kogan BA
The Urological Institute of Northeastern New York, and the Division of Urology, Department of Surgery, and Department of Pathology, Albany Medical College, Albany, NY, USA
BJU Int. 2005; 96: 634-8

• Objective: To study apoptosis and proliferation in the testes of children with undescended testes; the degree to which undescended testes contributes to a patient’s ultimate fertility is debatable, but undescended testes have fewer germ cells, and some have proposed that apoptosis is an important cause.
• Patients and Methods: Testis biopsies were taken at the time of orchidopexy in a consecutive series of children undergoing surgical repair for undescended testes. Immunohistological techniques were used to detect apoptosis and proliferation, and the numbers of cells undergoing apoptosis or proliferation per 50 seminiferous tubules were recorded.
• Results: Inguinal testes had less apoptosis than abdominal testes, with a mean (sd) of 0.71 (1.31) vs 1.63 (1.95) apoptotic cells per 50 seminiferous tubules (P < 0.02). Similarly, there was less apoptosis in children aged > 1 years than in children aged < 1 years (0.68 (1.40) vs 1.35 (1.56); P < 0.03). Proliferation was very limited in all cryptorchid testes. In contrast to cryptorchid testes, five autopsy controls had many more apoptotic cells, (10.60 (1.34) per 50 seminiferous tubules), and many more proliferating cells, (8.40 (6.43) per 50 seminiferous tubules).
• Conclusion: In contrast to animal studies, neither apoptosis nor proliferation was common in undescended testes from 6 months of age onward. However, apoptosis was more common in abdominal testes and in children aged < 1 year. It is likely that, if substantial apoptosis occurs in human undescended testes, it occurs before 6 months of age.
  
  
• Editorial Comment
  Apoptosis has been implicated in testicular germ cell loss in experimental models of cryptorchidism. Using the rat as an experimental model, it was demonstrated that apoptosis is the predominant mechanism of germ cell death rather than atrophy and necrosis in cryptorchidism (1,2). The mechanisms of germ cell apoptosis have been associated with oxidative stress or testicular exposure to elevated temperature, and there are evidence that endothelial nitric oxide synthase plays a functional role in mouse spermatogenesis in cryptorchidism-induced apoptosis (3).
  In the present elegant and well designed study, doctor Kogan and his group, by the first time, showed us that surprisingly and different from animal studies, neither apoptosis nor proliferation was common in undescended testes from children with more than 6 months of age. The authors discussed that this unexpected result is probably due to the timing of the biopsies, as significant apoptosis might have taken place before the typical time of surgical intervention (6 months).

References
1. Kocak I, Dundar M, Hekimgil M, Okyay P: Assessment of germ cell apoptosis in cryptorchid rats. Asian J Androl. 2002; 4: 183-6.
2. DeFoor WR, Kuan CY, Pinkerton M, Sheldon CA, Lewis AG: Modulation of germ cell apoptosis with a nitric oxide synthase inhibitor in a murine model of congenital cryptorchidism. J Urol. 2004; 172(4 Pt 2): 1731-5; discussion 1735.
3. Ishikawa T, Kondo Y, Goda K, Fujisawa M: Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. J Androl. 2005; 26: 281-8.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil