Apoptotic cell death in the normal and cryptorchid human testis: The effect of human chorionic gonadotropin on testicular cell survival

Cryptorchidism is associated with histologic changes in the human testis apparent by 2 y of age. The mechanism accounting for these changes is still unknown. To clarify whether apoptosis plays a role in human cryptorchidism, we evaluated its occurrence in cryptorchid testes of 73 prepubertal boys, 43 of whom had received human chorionic gonadotropin (hCG) treatment. The histologic samples in our study included both scrotal and inguinal testes. Using an in situ apoptosis detection method, we were able to demonstrate that both interstitial cells and germ cells were affected and that the specific germ cells undergoing apoptosis were exclusively spermatogonia. Apoptosis in situ was further seen in both scrotal and inguinal testes; in scrotal testes the numbers of apoptotic spermatogonia were 170% of those seen in the cryptorchid testes (p < 0.05). Analysis of apoptotic DNA fragmentation from isolated DNA of a few selected biopsy samples served to validate our in situ findings. The amount of germ cell apoptosis analyzed during the Ist mo after hCG treatment was increased in both scrotal and inguinal testes compared with the amount before treatment (p < 0.001). But after the Ist mo it returned to the initial level, suggesting that hCG (and/or androgen) withdrawal increases germ cell apoptosis in the human testis. Our findings lead to the conclusion that apoptosis is a hormonally controlled, normal phenomenon in a human prepubertal testis and that cryptorchidism decreases its occurrence by reducing the number of germ cells capable of undergoing apoptosis.