Apoptotic degeneration of germ cells in cryptorchid testis is associated with an increased level of
reactive oxygen species, and may be prevented by
antioxidant treatment. The objective of this study was to investigate whether
xanthine oxidase inhibitors could confer such protection.
Unilateral cryptorchidism was surgically induced in the immature rats, which were then left untreated or treated with
xanthine oxidase inhibitors, and the testes were evaluated 7 days after the operation. In the control group, the weight of the cryptorchid testis was decreased to 47% of that of the contralateral scrotal testis. However, administration of a
xanthine oxidase inhibitor
allopurinol (> or = 1 mg/kg/day) significantly attenuated
weight reduction of the cryptorchid testis (68-77% of the contralateral scrotal testis, P < 0.01 versus control). Another highly specific
xanthine oxidase inhibitor,
BOF-4272, also attenuated
cryptorchidism-induced testis regression. The effects of
allopurinol were associated with decreased apoptosis in germ cells as evaluated by in-situ staining of fragmented
DNA. In testicular cells cultured at 37 degrees C, either
allopurinol or
BOF-4272 prevented DNA cleavage characteristic of apoptosis. In conclusion,
xanthine oxidase inhibitors can inhibit germ cell apoptosis induced by experimental
cryptorchidism, and may be considered for treatment of
male infertility associated with heat stress.