Reproductive effects of the anti-cancer drug procarbazine in male rats at different ages.

Rats aged 10 days (Exp. A), 45 days (Exp. B) and 70-90 days (Exp. C) were given procarbazine intraperitoneally at doses of 30 mg/kg/day for 5 or 9 weeks (Exps A, B, C), or by gavage at doses of 5 mg/kg/day (equivalent to the therapeutic dose in man) and 50 mg/kg/day, for 9 weeks (Exp. B). A significant mortality rate was noted in immature rats (Exp. A) and in animals receiving 50 mg/kg/day orally (Exp. B). In all groups the rate of body weight gain and the weights of the testes and epididymides were reduced. Procarbazine produced disruption of the normal spermatogenetic architecture that was very severe or total in immature rats (Exp. A) and in rats given the drug at 30 mg/kg/day for 9 weeks and the highest dose (50 mg/kg) in Exp. B. Disruption of spermatogenesis was only partial in the other experimental groups. The number of Sertoli cells was not affected by the different treatments, but a Sertoli cell dysfunction (vacuolization, decreased ABP and elevated FSH concentrations), most probably secondary to germ cell degeneration, was demonstrated in those rats presenting the most severe disruption of spermatogenesis (Exp. B: i.p. and gavage, 50 mg/kg for 9 weeks). Leydig cells, always present in the interstitium, were moderately affected (decrease in serum testosterone values) in some groups at all ages whereas epididymal sperm reserves were decreased after 9 weeks (Exp. B: 30 mg/kg, i.p.; 5 and 50 mg/kg, gavage). Moreover, there was a marked fall in the number of fetuses per female mated by males in all experimental groups. We conclude that the effects of procarbazine on male reproductive function were independent of the route of administration, greater before puberty and proportional to the dose administered as well as to the duration of the treatment.