Enhancement of A spermatogonial proliferation and differentiation in irradiated rats by gonadotropin-releasing hormone antagonist administration

The initial changes in the numbers, proliferation, and differentiation of A spermatogonia in irradiated rats after the administration of a GnRH antago nist, which is known to induce differentiation in this system, were investi gated. LBNF1 rats were given 6 Gy of gamma-irradiation; some were treated w ith the GnRH antagonist Cetrorelix beginning 15 weeks after irradiation. Al though the spermatogonia in the irradiated rats without hormone treatment c ontinue to proliferate (labeling and mitotic indexes of 24% and 18%, respec tively), they underwent apoptosis (apoptotic indexes of 21% by the terminal transferase-mediated end labeling assay and 9% by nuclear morphology), res ulting in a constant number of A spermatogonia. Whole mount analysis of clo nes of A spermatogonia revealed that larger clones were more likely to unde rgo apoptosis than mitosis. Hormone administration decreased the intratesti cular testosterone concentration to 6% of the level in irradiated rats with in 1 week. Concomitantly, there was a decrease in spermatogonial apoptotic indexes to 43% of levels in irradiated-only rats, leading to an increases i n their numbers by 150%, their diameters by 11%, and their labeling indexes by 31%. The sizes of the mitotic clones gradually increased, and clones of more than eight cells appeared at week 3 of hormone treatment. A spermatog onial differentiation began at week 4, and by week 6.6, differentiation occ urred in 30% of the tubules. Thus, suppression of intratesticular testoster one by the GnRH antagonist may be responsible for the immediate changes in spermatogonial numbers and kinetics, but several additional steps are requi red before differentiation begins, which did not occur until week 4.