Cryptorchidism rescues spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice

Male mice homozygous for jsd mutation undergo an initial wave of spermatogenesis, but spermatogonial differentiation ceases a few weeks after birth; at that point the tubules show only type A spermatogonia and Sertoli cells. To test whether testicular descent into the scrotum contributes to the block in spermatogonial differentiation, jsd mutant (jsd/jsd) mice were bilaterally cryptorchidized at the age of 4 wk. Surprisingly, 8 wk later, germ cell differentiation was maintained in 98% of the tubules, a rate that fell to 13.5% in mice without surgery. The testis weight and the degree of spermatogenesis in cryptorchidized normal (jsd/+) and jsd mutant mice were almost identical. Furthermore, germ cell differentiation was also restored in almost all the tubules in 20-wk- and 70-wk-old jsd mutant testis unilaterally cryptorchidized 8 wk earlier, whereas the contralateral scrotal testis in these mice showed differentiation in only 6% of tubules. In irradiated LBNF1 rats, which have a block in spermatogonial differentiation similar to that in jsd mutant mice, unilateral cryptorchidism produced a small but significant increase in the percentage of differentiated tubules. In both of these models, the intratesticular levels of testosterone in the cryptorchidized testes were still above the physiological range, and the serum testosterone and LH levels were unchanged after bilateral or unilateral cryptorchidization. Cryptorchidism also did not alter serum FSH levels after bilateral and unilateral cryptorchidism in jsd mutant mice and irradiated rats, respectively. We conclude that cryptorchidism reverses the phenotype in jsd mutant mice. The findings show for the first time that spermatogenesis in rodents, and spermatogonial differentiation in particular, is sensitive to reduced scrotal temperature. Furthermore, we conclude that in jsd mutant mice spermatogonial differentiation is inhibited by testosterone only at the normal scrotal temperature.