SUPPRESSION OF MOUSE SPERMATOGENESIS BY A GONADOTROPIN-RELEASING-HORMONE ANTAGONIST AND ANTIANDROGEN - FAILURE TO PROTECT AGAINST RADIATION-INDUCED GONADAL DAMAGE

A combined GnRH antagonist (Nal-Glu) and antiandrogen (flutamide) trea tment was used to suppress mouse spermatogenesis in an attempt to enha nce recovery from stem cells after irradiation, as observed previously in the rat. Two weeks of treatment suppressed the intratesticular tes tosterone concentration to 10% of the control value, decreased testicu lar weight to 16% of the control value, and sperm count 2600-fold. Sup pression was at least as great as that produced in the rat by Nal-Glu- flutamide. Testicular weights, sperm counts, and histology were indist inguishable from those in normal controls 45 days after the end of the treatment. Despite the suppression of spermatogenesis, the treatment did not enhance recovery of spermatogenesis after damage produced by a 10-Gray dose of radiation; 45 days after irradiation, testicular weig ht, sperm head counts, and repopulation indexes were as low as in the mice that received no hormone treatment. In contrast to the situation in the rat, after irradiation of mice, almost no A spermatogonia were found in the 80% nonrepopulating tubules, indicating that nearly all A spermatogonia remaining after irradiation were capable of differentia tion. This absence of A spermatogonia that fail to differentiate in th e mouse is proposed as the reason for failure to protect against radia tion-induced gonadal damage by hormone treatment.