Effects of maternal nicotine exposure on branching morphogenesis of mouse fetal lung: in vivo and in vitro studies.

Epidemiological evidence suggests that premature infants born to mothers who smoke have a lower incidence of neonatal respiratory distress syndrome. The mechanism has been proposed to be due to increased lung maturity. This in vivo study investigated the effect of maternal nicotine on lung development by evaluating the airway branching morphogenesis (ABM) in mice fetuses. Nicotine (0, 2 and 3 mg/kg/day) was administered intraperitoneally to pregnant mice from gestation day 9 to day 12 (4 days). ABM was determined on day 13 by photomicrographic analysis. The results revealed a significant reduction in ABM in the higher dose nicotine group. The mean number of airway branches was 3.7 +/- 0.1/lobe for the 3 mg/kg/day group, which was smaller than 4.6 +/- 0.2/lobe for the 2 mg/kg/day nicotine group, and 4.4 +/- 0.1/lobe for the control group (F = 9.4, p < 0.001). The mean number of buds was significantly smaller in both the 2 mg/kg/day group and the 3 mg/kg/day group (8.7 +/- 0.5/lobe, 9.0 +/- 0.4/lobe vs. 12.3 +/- 0.4/lobe in the control group, F = 20.3, p < 0.001). For the in vitro study, fetal lung lobes were isolated at the 12th gestation day. The lung explants were cultured in nicotine (0, 30, 60 ng/ml) for 48 hours; there were no differences in all the groups. The results do not support the hypothesis that nicotine stimulates fetal lung ABM either in vivo or in vitro.