Shinohara O, Henrich R T, Morishima A
Biol Reprod. 1983 Oct;29(3):663-70. doi: 10.1095/biolreprod29.3.663.
The effects of chronic administration of delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marihuana, on embryogenesis were investigated in the mouse treated with THC prior to sexual maturation. The study was designed to imitate the prolonged abuse of marihuana by sexually immature and adolescent girls. Female Swiss-Webster mice were injected, intraperitoneally, with THC 5 mg/kg per day or with the vehicle for 21 consecutive days, starting on the 30th day of life, which is prior to their sexual maturation. The dose of THC was approximately equivalent to that absorbed by a man smoking 1 to 2 marihuana cigarettes per day. Superovulation was then induced, and the mice were mated with untreated males. Ova were recovered from the oviducts just prior to the first cleavage division, and at about the time of the second cleavage division. The incidence of degenerative ova increased from 13.6% in the controls to 19.1% in the THC-treated group (P less than 0.001) at the time of the second cleavage division, but there was no difference in the incidence of morphologically abnormal ova between the two groups just prior to the first cleavage division. The rate of successful completion of the first cleavage division, but not the second cleavage division, was adversely affected by THC, resulting in accumulation of morphologically abnormal ova at the later stage. In view of the known disruptive effect of THC on the process of cell division, it was postulated that THC might have adversely affected meiosis, leading to the inability of the ova to undergo the first cleavage division.
在性成熟前用δ-9-四氢大麻酚(THC,大麻的主要精神活性成分)对小鼠进行慢性给药,研究其对胚胎发生的影响。该研究旨在模拟性不成熟和青春期女孩长期滥用大麻的情况。从出生后第30天(即性成熟前)开始,对雌性瑞士韦伯斯特小鼠连续21天腹腔注射5mg/kg的THC或溶剂。THC的剂量大约相当于每天吸1至2支大麻烟的人所吸收的剂量。然后诱导超排卵,并将小鼠与未处理的雄性小鼠交配。在第一次卵裂前和第二次卵裂时从输卵管中回收卵子。在第二次卵裂时,退化卵子的发生率从对照组的13.6%增加到THC处理组的19.1%(P<0.001),但在第一次卵裂前两组形态异常卵子的发生率没有差异。THC对第一次卵裂的成功完成率有不利影响,但对第二次卵裂没有影响,导致后期形态异常卵子的积累。鉴于已知THC对细胞分裂过程有破坏作用,推测THC可能对减数分裂有不利影响,导致卵子无法进行第一次卵裂。