Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice
Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice
复制标题
DOI：
10.1002/jat.3631
复制
发表时间：
2018-09-01
影响因子：
3.3
通讯作者：
Mazaro-Costa, Renata
中科院分区：
文献类型：
--
作者：
Carvalho, Renata K.;Santos, Monaliza L.;Mazaro-Costa, Renata
患有频繁和严重癫痫发作的儿童和成人对标准治疗（如卡马西平，苯妥英钠和丙戊酸盐）没有反应，长期以来一直将大麻二酚（CBD）作为抗惊厥药物。然而，长期使用该药物对生殖的安全性尚未得到充分研究。本研究旨在评估慢性CBD暴露对男性生殖系统的影响。将CBD以每天15和30 mg kg（-1）的剂量口服给药于21日龄的雄性瑞士小鼠（CBD 15和30组，分别），对照组接受向日葵籽油，连续34天。35天恢复期后，评价以下参数：生殖器官重量、睾酮浓度、精子发生、组织形态计量学、每日精子产量及其形态。CBD 30组的总循环睾酮减少了76%，但仍在生理正常范围内（240-1100 ng dl（-1））。CBD处理诱导精子发生的阶段I-IV和V-VI的频率显著增加，阶段VII-VIII和XII的频率降低。仅在CBD 30组中观察到支持细胞数量的显著减少。在两个CBD组中，附睾尾部的精子数量减少了38%，精子头部异常，在鞭毛的内侧区域观察到细胞质液滴。这些结果表明，慢性CBD暴露与男性生殖系统的变化有关，表明其生殖毒性。
Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21-day-old male Swiss mice at doses of 15 and 30 mg kg(-1) daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days. After a 35day recovery period, the following parameters were evaluated: weight of reproductive organs, testosterone concentration, spermatogenesis, histomorphometry, daily sperm production and its morphology. The CBD 30 group had a 76% decrease in total circulating testosterone, but it remained within the physiological normal range (240-1100 ng dl(-1)). CBD treatment induced a significant increase in the frequency of stages I-IV and V-VI of spermatogenesis, and a decrease in the frequency of stages VII-VIII and XII. A significant decrease in the number of Sertoli cells was observed only in the CBD 30 group. In both CBD groups the number of spermatozoa in the epididymis tail was reduced by 38%, sperm had head abnormalities, and cytoplasmic droplets were observed in the medial region of flagellum. These results indicated that chronic CBD exposure was associated with changes in the male reproductive system, suggesting its reproductive toxicity.