Increased apoptosis of spermatogenic cells in cryptorchidism rat model and its correlation with transforming growth factor beta type II receptor.
OBJECTIVE
To investigate the role played by transforming growth factor beta receptor II (TGFbetaRII) 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, TGFbetaRII/smad, and TGFbetaRII/mitogen-activated protein kinase activation were explored by hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and western blot analysis, respectively. TGFbetaRII was knocked down in GC-2 spg cells and the cells were then treated with hyperthermia. Western blot analysis was performed to detect TGFbetaRII, 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 TGFbetaRII and smad2 expression increased. Phosphorylation of smad2, smad3, and p38 and cleavage of caspase-3 increased in UUTs. TGFbetaRII 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 TGFbetaR/smad and TGFbetaR/mitogen-activated protein kinase pathways.
Yuan
Jian-Lin
JL
Department of Urology Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaan'xi, China.
Zhang
Yun-Tao
YT
Wang
Yong
Y
D000818:Animals; D017209:Apoptosis; D003456:Cryptorchidism / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D013090:Spermatocytes / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II