Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Physiology and Pharmacology

Collaborative Specialization

Developmental Biology

Supervisor

Feng, Qingping

2nd Supervisor

Jones, Douglas L.

Co-Supervisor

Abstract

Congenital heart defects 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 much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in both congenital heart defects and hypoplastic coronary arteries at a significant incidence of 43% and 31%, respectively. Moreover, MNE resulted in altered gene expression of key cardiogenic regulators and higher levels of oxidative stress in the embryonic hearts. Myocardial cell proliferation and epithelial-to-mesenchymal transition was lower with MNE.In summary, MNE resulted in a higher incidence of congenital heart defects and coronary artery defects. To our knowledge, this study demonstrated, for the first time, that maternal nicotine exposure in a mouse model induces a range of congenital heart defects, and impairs coronary artery vasculature. These findings could provide insight into the dangers of nicotine replacement therapy for the offspring during pregnancy.

Summary for Lay Audience

Congenital heart defects 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 much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in both congenital heart defects and coronary artery defects at a significant incidence of 43% and 31%, respectively. Moreover, MNE resulted in altered gene expression of important regulator of heart development and higher levels of oxidative stress in the embryonic hearts.In summary, MNE resulted in a higher incidence of congenital heart defects and coronary artery defects. To our knowledge, this study demonstrated, for the first time, that maternal nicotine exposure in a mouse model induces a range of congenital heart defects, and impairs coronary artery vasculature. These findings could provide insight into the dangers of nicotine replacement therapy for the offspring during pregnancy.

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