Effects of tobacco smoke inhalation on the developing mouse embryo and fetus.

Pregnant C57BL or mutant curly tail mice were exposed to tobacco smoke in a smoking machine for 10 min, three times a day, either on the day of conception (day 0) and days 1 and 2, or on days 3, 4, and 5, or from day 0 through day 17. In the first two cases, the embryonic development was subsequently assessed on day 9. Both periods of exposure were associated with a dose-related retardation in embryonic growth, but it was more marked with exposure on days 0, 1, and 2. It would seem, therefore, that even brief episodes of maternal smoking are detrimental to the very early embryo, and even if smoking is stopped, the effects persist at least for some days and there is no immediate catch-up growth. In the mice exposed continuously for 17 days, the fetuses were studied on day 18: there was a significant reduction in fetal body weight in both types of mice. There was also a reduction in the number of skeletal ossification centres, showing that additionally, there was developmental delay. In C57BL mice, one rib abnormality occurred, but no major congenital malformations; however, in the curly tail mutants, 60% of which normally have a curly tail or an open neural tube defect, there was a modest increase in the frequency of open spina bifida and exencephaly. A few minor rib abnormalities also occurred, and one case of cleft lip with cleft palate. These results indicate that tobacco smoke, while detrimental to the developing fetus, is not a potent teratogen in the mouse, but that it may have minor effects in those individuals genetically predisposed to an abnormality. This may have implications for humans, and may explain the generally inconclusive findings regarding congenital malformations in the children of women who smoke during pregnancy. In all experiments, the detrimental effects were seen with both higher tar cigarettes (tar and nicotine yields: 12.9 and 1.19 mg/cigarette, respectively) and lower tar cigarettes (4.8 and 0.54 mg/cigarette respectively), so tobacco modification is not really beneficial to the developing fetus.