Expression and roles of survivin in experimental rat cryptorchidism.
Objectives: Cryptorchidism is one of the most common causes of infertility in men. In cryptorchidism, although it has been established that there is spermatogenetic disorder because of increasing apoptosis, the molecular mechanisms responsible have not yet been fully elucidated. The production of sperm is regulated by a balance between proliferation and apoptosis. Survivin is one of the inhibitors of the apoptosis protein (IAP) and its expression seems to correlate with not only apoptosis but also proliferation during spermatogenesis. We established experimental cryptorchid rats and investigated expression and the possible role of survivin in the cryptorchid testis. Methods: Eight-week-old male Sprague-Dawley rats, weighing approximately 260-300g, were maintained, and experimental cryptorchid rats were established from among them. The animals were divided into four groups. One group was sacrificed to be evaluated without any surgical intervention (normal control, n=5). The other three groups were sacrificed following 3, 7 and 14 days of cryptorchidism (n=3×5). Johnsen's score for the rat and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was used for evaluation of spermatogenesis and apoptosis, respectively. Survivin expression in experimental cryptorchidism was examined by the reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. Results: Apoptotic germ cells peaked early after cryptorchidism surgery (day 3) and testicular weight and Johnsen's score decreased progressively with longer periods of cryptorchidism. In the normal control and sham-operated testes, abundant expression of survivin protein was observed. On the other hand, the expression in cryptorchid testes decreased progressively with longer periods of cryptorchidism. As for immunohistochemistry, nuclear and cytoplasmic localization was observed in the normal control and sham-operated testes and the cytoplasmic stain did not decrease. In the cryptorchid testes, however, the nuclear stain became progressively stronger. Conclusion: Survivin expression in testes could be used in the evaluation of spermatogenic disorders such as cryptorchidism.