Experimental Cryptorchidism Induces Testicular Germ Cell Apoptosis by p53-Dependent and -Independent Pathways In Mice

Cryptorchidism is associated with male infertility: germ cell loss occurs by apoptosis in response to elevated temperature. Since the tumor suppressor p53 is highly expressed in the testis and is known to induce apoptosis, an investigation was undertaken to establish whether heat stress causes p53-mediated germ cell apoptosis. Using a mouse model of experimental unilateral cryptorchidism, it was observed that testicular weight reduction, germ cell loss, and DNA fragmentation all began in the cryptorchid testes on Day 6-7 in wild-type mice. In contrast, these changes were delayed by 3 days in p53-/- mice. These results suggest that abdominal heat stress induces germ cell loss through two apoptotic pathways: a p53-dependent pathway responsible for the initial phase of germ cell apoptosis, and a p53-independent pathway that accounts for subsequent apoptosis.