Prenatal nicotine increases pulmonary alpha 7 nicotinic receptor expression and alters fetal lung development in monkeys

It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illness es after birth. To determine if this is the direct result of nicotine inter acting with nicotinic cholinergic receptors (nAChRs) during lung developmen t, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduc ed surface complexity of developing alveoli. Immunohistochemistry and in si tu alpha-bungarotoxin (alpha BGT) binding showed that alpha 7 nAChRs are pr esent in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macr ophages, and pulmonary neuroendocrine cells (PNEC). As detected both by imm unohistochemistry and by alpha BGT binding, nicotine administration markedl y increased alpha 7 receptor subunit expression and binding in the fetal lu ng. Correlating with areas of increased alpha 7 expression, collagen expres sion surrounding large airways and vessels was significantly increased. Nic otine also significantly increased numbers of type II cells and neuroendocr ine cells in neuroepithelial bodies. These findings demonstrate that nicoti ne can alter fetal monkey lung development by crossing the placenta to inte ract directly with nicotinic receptors on non-neuronal cells in the develop ing lung, and that similar effects likely occur in human infants whose moth ers smoke during pregnancy.