Effects of Chronic Administration of Delta-9-Tetrahydrocannabinol on Early Embryogenesis of the Mouse

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Abstract
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, i.p., 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 1-2 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 1st cleavage division, and at about the time of the 2nd cleavage division. The incidence of degenerative ova increased from 13.6% in the controls to 19.1% in the THC-treated group (P < 0.001) at the time of the 2nd cleavage division, but there was no difference in the incidence of morphologically abnormal ova between the 2 groups just prior to the 1st cleavage division. The rate of successful completion of the 1st cleavage division, but not the 2nd 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 the on the process of cell division, THC might have adversely affected meiosis, leading to the inability of the ova to undergo the 1st cleavage division.