In-utero exposure to alcohol and nicotine alters the fetal lung innate immunity and development

摘要

Despite the evidence that alcohol and cigarette smoke have harmful effects on the developing fetus, alcohol consumption and smoking during pregnancy remains a common behavior among women. Fetal exposure to alcohol can result in numerous developmental abnormalities referred to as fetal alcohol spectrum disorder (FASD). Fetal exposure to cigarette smoke is related to premature birth and low birth weight for gestational age. Recent evidence suggests, however, that both alcohol and cigarette smoke may alter the fetal lung development and immunity and therefore predispose infants to respiratory infections. The purpose of this study was to establish new, advantageous animal models for fetal exposure to alcohol and nicotine; to determine if in-utero exposure to alcohol and nicotine alters fetal lung innate immune components, primarily surfactant proteins A and D (SP-A and SP D, respectively); and finally to determine the possible mechanism by which alcohol alters the fetal lung development and immunity. In this study, we established new sheep animal models for fetal exposure to alcohol and nicotine. We demonstrated that exposure to low levels of alcohol during the last trimester of pregnancy decreases SP-A gene expression in lambs born prematurely and SP-A protein expression in full-term lambs. Exposure to alcohol did not alter SP-D protein or gene expression in pre-term or full-term lambs. In addition, exposure to low levels of nicotine during the last trimester of pregnancy decreases SP-A gene and protein expression in lambs born prematurely. Exposure to nicotine did not alter SP-D protein or gene expression in pre-term or full-term lambs. Finally, we demonstrated that alteration of SP-A expression in premature lambs exposed to alcohol in-utero could be attributed to the alcohol-related decreased expression of vascular endothelial growth factor (VEGF) in the fetal lung.In conclusion, our findings indicate that fetal exposure to alcohol and nicotine alters the fetal lung innate immunity and development which in part may explain alcohol and nicotine-related increased incidence of respiratory infections in neonates.