Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology

Supervisor

Dr. Qingping Feng

2nd Supervisor

Dr. Douglas L. Jones

Co-Supervisor

Abstract

Pregestational diabetes is a risk factor for birth defects, with diabetic women having a four times higher risk of producing children with congenital heart defects (CHDs). This is concerning because the prevalence of diabetes is growing at epidemic proportions. The purpose of this thesis is to investigate whether exercise can also reduce hyperglycemia-induced CHDs and determine the underlying mechanism. Endothelial nitric oxide synthase (eNOS) is a critical enzyme for normal cardiogenesis that can be upregulated with exercise in adult cardiovascular tissue. However, whether maternal exercise can regulate fetal eNOS and affect heart development has yet to be studied. In this thesis, a mouse model of streptozotcin-induced diabetes was used to generate a hyperglycemic gestational environment. Incidence of CHDs in offspring of diabetic mice was significantly reduced by maternal voluntary exercise from 63 to 31%. Fetal hearts also showed improved aortic and pulmonary valve remodeling compared to the non-exercised diabetic group. Diabetes-induced defects in coronary artery volume as well as capillary density were also rescued with exercise. Myocardial cell proliferation and epithelial-mesenchymal transition at E12.5 was significantly decreased with pregestational diabetes but recovered with maternal exercise. Embryonic gene expression of eNOS, as well as cardiogenic transcription factor Gata4 was restored to control levels with exercise in diabetic mice. These findings provide evidence that exercise may be a feasible intervention to lower the incidence of CHDs in the offspring of women with pregestational diabetes.

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