Fetal testosterone in mice: effect of gestational age and cannabinoid exposure

The effect of increasing gestational age and maternal exposure to cannabinoids on body weight, ano-genital distance and androgen concentration in fetal mice was examined. Body weight increased in both male and female fetuses from days 16 to 18 (the presence of a vaginal plug was considered to indicate day 1 of pregnancy), while ano-genital distances tended to increase faster in male than in female fetuses. The concentration of testosterone increased with age in fetuses of either sex. However, at day 16, there was a significant influence of fetal sex on testosterone concentration with two non-overlapping distribution, one above and one below 300 pg/g fetal tissue, correlating with male and female gender respectively. After day 16, male fetuses tended to have higher testosterone concentrations, but some values obtained in females did overlap. Treatment of female mice with delta 9-tetrahydrocannabinol, the main psychoactive ingredient of marihuana, from days 12 to 16 pregnancy caused a significant (P less than 0.01) increase in fetal deaths in utero. Cannabinol treatment had no effect on this parameter, but reduced body weight (P less than 0.02) in female fetuses, and increased ano-genital distance (P less than 0.05) in male fetal mice. The concentrations of testosterone and dihydrotestosterone were reduced in male but not in female fetuses. The results indicate that exposure to psychoactive or non-psychoactive constituents of marihuana suppresses testosterone levels in fetal as well as in immature and adult mice, as we have previously reported. Thus, maternal exposure to cannabinoids may interfere with the process of sexual differentiation in their male offspring as a result of decreased fetal androgen production.