Activation of NF-kappaB associated with germ cell apoptosis in testes of experimentally induced cryptorchid rat model.
OBJECTIVE
To evaluate the behavior of NF-kappaB in the cryptorchid testes, we investigated the testes of an experimentally induced cryptorchid rat model. Cryptorchid testes exhibit degenerative changes in the germinal epithelium with germ cell apoptosis, which results in future infertility. However, the mechanisms of apoptosis in the germ cells are multifactorial and have not been completely elucidated. NF-kappaB is a transcription factor considered to play an important role in the apoptosis of various cells.


METHODS
The cryptorchid rat model was generated by the administration of an antiandrogenic agent during the fetal period. The unilateral cryptorchid testes and contralateral descended testes were removed at 7-10 weeks after birth, and histopathologic examination and Western blot analysis were performed. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, and the expression of NF-kappaB and IkappaB proteins was investigated using immunohistochemistry.


RESULTS
In the present model, spermatogenesis was arrested at the spermatid differentiation stage, and elongated spermatids or spermatozoa were not detected. Apoptosis was noted predominantly in the primary spermatocytes, and Sertoli cells and Leydig cells did not undergo apoptosis. On immunohistochemistry, NF-kappaB signals were increased and focused on the nucleus of the germ cells in the cryptorchid testes, consistent with TUNEL-positive cells. On Western blot analysis, the NF-kappaB and IkappaB proteins were detected more intensely in the cryptorchid testes.


CONCLUSIONS
The activation of NF-kappaB was associated with germ cell apoptosis in experimentally induced cryptorchid testes, suggesting that NF-kappaB has certain roles in germ cell apoptosis. The results of the present study may guide toward new therapeutic possibilities for the impairment of spermatogenesis in patients with cryptorchidism.
Mizuno
Kentaro
K
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Hayashi
Yutaro
Y
Kojima
Yoshiyuki
Y
Nakane
Akihiro
A
Tozawa
Keiichi
K
Kohri
Kenjiro
K
D000818:Animals; D017209:Apoptosis; D003456:Cryptorchidism / Q000473:pathology*; D004195:Disease Models, Animal; D005854:Germ Cells; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016328:NF-kappa B