Effects of cefamandole on spermatogenic development of young CD rats

The testicular toxicity of cefamandole, a beta-lactam antibiotic with an N-methylthiotetrazole side chain, was evaluated in neonatal rats. Cefamandole caused delayed maturity of the germinal epithelium of neonatal rats when given on Postpartum Days 6 through 36. In rats given daily subcutaneous injections of 1000 mg/kg during this period, the most mature germinal cells were acrosome phase spermatids, whereas control rats had spermatids in the maturation phase. In studies of specific developmental phases, the effect of 1000 mg/kg daily cefamandole was primarily on the initial waves of spermatogonia during the period of rapid development (Postpartum Days 4 through 13). In animals treated from birth to Postpartum Day 8 and evaluated sequentially on Postpartum Days 5 through 9, there were no morphologically discernible effects on the transformation of gonocytes to immature spermatogonia, but there were slight degenerative changes in the first waves of developing spermatogonia. Cefamandole, 1000 mg/kg daily, given Postpartum Days 14 through 18 during the initial phase of spermatocyte development, also caused a slight degenerative change of the initial waves of pachytene spermatocytes. The significance of the findings in neonatal rats is unknown because differences in spermatogenic development between rat and human preclude direct extrapolation of the effects of cefamandole in neonatal rats to effects in humans.