Increased Apoptosis of Spermatogenic Cells in Cryptorchidism Rat Model and Its Correlation With Transforming Growth Factor Beta Type II Receptor

• Published in: Urology (Ridgewood, N.J.) Vol. 75; no. 4; pp. 992 - 998
• Main Authors: Yuan, Jian-Lin, Zhang, Yun-Tao, Wang, Yong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2010
• Subjects: Animals; Apoptosis; Cryptorchidism - metabolism; Cryptorchidism - pathology; Disease Models, Animal; Male; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases - physiology; Rats; Receptors, Transforming Growth Factor beta - physiology; Smad Proteins - metabolism; Spermatocytes - pathology; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2009.05.020

Objectives To investigate the role played by transforming growth factor beta receptor II (TGFβRII) in cryptorchidism-induced spermatocyte apoptosis. Methods A unilateral cryptorchidism rat model was surgically established in 20-day-old male SD rats. Testis samples were collected 0, 4, 7, 14, and 21 days after surgery. Histologic changes, apoptosis, TGFβRII/smad, and TGFβRII/mitogen-activated protein kinase activation were explored by hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and western blot analysis, respectively. TGFβRII was knocked down in GC-2 spg cells and the cells were then treated with hyperthermia. Western blot analysis was performed to detect TGFβRII, the phosphorylation status of smad2, smad3, and p38 and the cleavage status of caspase-3. Results Surgically induced cryptorchidism significantly impaired testis growth and spermatogenesis in unilateral undescended testes (UUTs) compared with contralateral descended testes 7, 14, and 21 days after surgery. The mean apoptotic index was significantly higher in UUTs than in contralateral descended testes. Western blot analysis showed that TGFβRII and smad2 expression increased. Phosphorylation of smad2, smad3, and p38 and cleavage of caspase-3 increased in UUTs. TGFβRII knockdown in GC-2 spg cells reduced hyperthermia-induced apoptosis by inhibiting smad2, smad3, and p38 phosphorylation as well as downstream caspase-3 cleavage. Conclusions Cryptorchidism lowered the growth rate of testes by inducing apoptosis, via a mechanism involving the activation of the TGFβR/smad and TGFβR/mitogen-activated protein kinase pathways.