An in vitro system for experimentally induced cryptorchidism.

Abstract

Cryptorchidism is one of the most common abnormalities of male sexual development, and is characterized by the failure of the testis to descend into the scrotum. Despite extensive studies of cryptorchidism over the past century, the mechanisms for temperature-induced germ-cell loss are not well understood. All of the main cell types in the testis are believed to be affected by the elevated testis temperature induced by cryptorchidism. The cooler temperature in the special environment of the scrotum is required for maintaining optional conditions for normal spermatogenesis. Many studies reported that experimentally induced cryptorchidism caused germ cell apoptosis and suppressed spermatogenesis. However, other factors including hormones must also be examined for cryptorchidism. To explore the mechanism for cryptorchidism, invitro cultures of testes have been used, but complete spermatogenesis using invitro methods was not accomplished until 2011. In 2011, Sato etal. (Nature, 471, 504-507) reported the invitro production of functional sperm in cultured neonatal mouse testes. Using this invitro system, for the first time, we report that spermatogenesis was abrogated at 37°C, in accordance with invivo surgery-mediated cryptorchidism, while spermatogenesis proceeded at 34°C in cultured testes. This result clearly showed that temperature is the sole determinant of cryptorchidism. Moreover, we found that spermatogenesis was arrested before early spermatocytes at 37°C. In conclusion, using our invitro system, we have demonstrated that (1) temperature is the determining factor for cryptorchidism, and (2) higher temperature (37°C) suppresses DNA synthesis in spermatogenesis.