George V K, Li H, Teloken C, Grignon D J, Lawrence W D, Dhabuwala C B
Department of Urology, Wayne State University, Detroit, Michigan 48201, USA.
J Urol. 1996 Jan;155(1):327-31.
This study was conducted to investigate the effects of long-term administration of cocaine on spermatogenesis and fertility in adult male rats.
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.
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).
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.
本研究旨在调查长期给予可卡因对成年雄性大鼠精子发生和生育能力的影响。
30日龄雄性Sprague-Dawley大鼠每日或每周两次（周末组，周六和周日给予可卡因）给予盐酸可卡因（15毫克/千克体重，相当于重度可卡因使用者的平均单次剂量），在接触该药物100天和150天后与经证实可怀孕的雌性大鼠交配。评估怀孕率和窝仔出生体重。测量所有成年大鼠的血清睾酮、卵泡刺激素和黄体生成素水平。对睾丸进行形态学分析，评估定量和定性组织学参数，以评估可卡因对精子发生各个阶段的影响。
治疗100天后，每日接受可卡因治疗的大鼠怀孕率仅为33%，而对照组为86%（p<0.05）。在接触可卡因150天的大鼠中，怀孕率为50%，而对照组为100%（p<0.05）。每日接受可卡因治疗组的后代出生体重比对照组低10%（p<0.05）。睾丸和附睾的重量不受可卡因暴露的影响。形态计量学分析显示，可卡因治疗组（每日可卡因组和每周两次可卡因组）与其各自的对照组之间存在显著差异。与各自的对照组相比，每日和每周两次可卡因组的生精小管平均直径减小。治疗组与其对照组之间的这些差异具有统计学意义（p<0.05）。同样，可卡因治疗组的生精上皮厚度比对照组薄（p<0.05）。每日和每周两次可卡因组中退化细胞的数量均多于对照组。此外，每日和每周两次可卡因组中VII期精子细胞的数量均减少，差异具有统计学意义（p<0.05）。
我们的研究结果表明，对青春期前雄性大鼠长期给予可卡因对其睾丸功能有深远影响。即使每周给药两次，对精子发生也有显著的不利影响，尽管该组的生育能力并未降低。这些研究结果证实，对雄性大鼠长期给予可卡因会对精子发生和生育能力产生有害影响。
