Coronary artery formation in the offspring of female mice with pregestational diabetes

Abstract

Women with pregestational diabetes have a 5-fold increased risk of congenital heart defects in their offspring. Major congenital heart diseases involving malformation of ventricles, atria and great arteries have been reported in humans and diabetic animal models. Whether the coronary artery formation is affected by maternal diabetes remains elusive. We investigated coronary artery formation in the offspring of mice with pregestational diabetes. Adult C57BL/6 female mice were treated with streptozotocin to induce diabetes. One week later, they were bred with C57BL/6 males and their offspring was harvested at E9.5, E12.5 and P1. Hearts were evaluated for coronary artery morphology and immunostained for Wilm's tumor-1 protein to study changes in proepicardium organ (PEO) and the epicardium. Our results showed that coronary arteries total volume was significantly decreased in the offspring of diabetic mice at P1. PEO at E9.5 was similar in size between the offspring of diabetic and non-diabetic mice. However, a significant reduction in the number of epicardial cells was observed in the diabetic offspring at E12.5. We conclude that pregeatational diabetes induces coronary artery malformation possibly by disrupting epicardial development, which is critical for formation of coronary arteries through epithelial to mesenchymal transformation. This research is supported by HSFO.