Maternal Nicotine Exposure Induces Congenital Heart Defects in the
Offspring of Mice
Abstract
Background and Purpose: Congenital heart defects (CHDs) are the
most prevalent birth defect, and maternal cigarette smoking is a known
risk factor. Nicotine replacement therapies are recommended to pregnant
women who smoke to aid in smoking cessation, as this alternative is
thought to be safer compared to cigarette smoking. However, these
products contain nicotine, and the safety of nicotine on the developing
heart is not well known. We examined the effects of maternal nicotine
exposure (MNE) during pregnancy on fetal heart development in mice.
Experimental Approach: C57BL/6 female mice were treated with
nicotine at 1.5 mg/kg/day using subcutaneous osmotic pumps and bred with
normal male mice. The effects of MNE on fetal hearts were analyzed.
Key Results: MNE resulted in CHDs and hypoplastic coronary
arteries in fetal mice at significant incidences of 43% and 31%,
respectively. CHDs included septal defects, atrioventricular septal
defects, double outlet right ventricles, thickened aortic and pulmonary
valves, isolated hypoplastic left ventricles, and ventricular
hypertrophy. Moreover, MNE resulted in altered gene expression of key
cardiogenic regulators and higher levels of oxidative stress in the
embryonic hearts. Fetal heart epicardial epithelial-to-mesenchymal
transition (EMT) was lower with MNE. Conclusions and
Implications: MNE results in a higher incidence of congenital heart
defects and coronary artery defects. These findings provide insight into
the dangers of nicotine replacement therapy to fetuses during pregnancy.