PROTECTION FROM RADIATION-INDUCED DAMAGE TO SPERMATOGENESIS BY HORMONE-TREATMENT

Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherap y. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesi s and protects spermatogonial stem cells from procarbazine-induced dam age, would also protect these cells from radiation. Adult male LBNF(1) rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Control s were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after i rradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the rep opulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in th e controls. Protection factors (dose-modifying factors) calculated fro m the dose-response curves were in the range of 1.5-2.2. Elucidation o f the mechanism of protection is essential to apply it to clinical sit uations. The fact that the spermatogonia are protected against radiati on as well as procarbazine indicates that the mechanism does not invol ve drug delivery or metabolism