Effects of long-term cocaine exposure on spermatogenesis and fertility in peripubertal male rats

Purpose: This study was conducted to investigate the effects of long-term administration of cocaine on spermatogenesis and fertility in adult male rats. Materials and Methods: Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg./kg. body weight, corresponding to an average single dose for a heavy cocaine user) either daily or twice weekly (weekend group, cocaine given on Saturday and Sunday) and mated with pregnancy-proven female rats after 100 and 150 days of exposure to the drug. Pregnancy rates and litter birth weights were evaluated, Serum testosterone, follicle stimulating hormone and luteinizing hormone levels were measured in all adult rats. Morphologic analysis of the testis entailed the evaluation of quantitative and qualitative histologic parameters to assess the effect of cocaine on various stages of spermatogenesis. Results: After 100 days of treatment, the rats receiving daily cocaine had a pregnancy rate of only 33% versus 86% for the controls (p <0.05). In rats exposed to cocaine for 150 days the pregnancy rate was 50% compared with 100% for controls (p <0.05). The birth weights of offspring from the group receiving daily cocaine was 10% less than that of controls (p <0.05). The weight of the testis and epididymis was not affected by cocaine exposure. Morphometric analysis showed significant differences between the cocaine-treated groups (both the daily cocaine and twice weekly cocaine groups) and their respective controls. The mean diameter of seminiferous tubules in the daily and twice weekly cocaine groups was reduced when compared with their respective controls. These differences between treated groups and their controls were statistically significant (p <0.05). Similarly the thickness of the germinal epithelium was less in the cocaine-treated groups than in the controls (p <0.05). Degenerating cells were more numerous in both daily and twice weekly cocaine groups than the controls, Furthermore, the number of step VII spermatids was reduced in both daily and twice weekly cocaine groups, a difference that was statistically significant (p <0.05). Conclusion: Our findings demonstrate that chronic administration of cocaine to peripubertal male rats has a profound effect on their testicular function. Even with twice weekly administration there was a significant adverse effect on spermatogenesis although this was not manifested by diminished fertility in this group. These findings confirm that chronic administration of cocaine to male rats can have a deleterious effect on spermatogenesis and fertility.