High Glucose Level Induces Cardiovascular Dysplasia During Early Embryo Development

Abstract

The incidence of gestational diabetes mellitus (GDM) has increased dramatically amongst multiethnic population. However, how gestational diabetes mellitus damages the developing embryo is still unknown. In this study, we used yolk sac membrane (YSM) model to investigate angiogenesis in the developing chick embryo. We determined that in the presence of high glucose, it retarded the growth and extension of the embryonic vascular plexus and it also reduced the density of the vasculature in yolk sac membrane model. Using the same strategy, we used the chorioallantoic membrane (CAM) as a model to investigate the influence of high glucose on the vasculature. We established that high glucose inhibited development of the blood vessel plexus and the blood vessels formed had a narrower diameter than control vessels. Concurrent with the abnormal angiogenesis, we also examined how it impacted cardiogenesis. We determined the myocardium in the right ventricle and left atrium were significantly thicker than the control and also there was a reduction in glycogen content in cardiomyocytes. The high glucose also induced excess reactive oxygen species (ROS) production in the cardiomyocytes. We postulated that it was the excess reactive oxygen species that damaged the cardiomyocytes resulting in cardiac hyperplasia.

Potential Role of Hyperglycemia in Fetoplacental Endothelial Dysfunction in Gestational Diabetes Mellitus

“…It has been reported that the majority of placentas from GDM pregnancies exhibit increased [22] or abnormal angiogenesis [23,24]. Our present data revealed that the placental weights from the GDM pregnancies were significantly increased compared with those of the normal healthy controls (Table 1).…”

Study of Regional Left Ventricular Longitudinal Function in Fetuses with Gestational Diabetes Mellitus by Velocity Vector Imaging

“…Gestational diabetes mellitus is a relatively common condition in pregnancy, especially in the second and the third trimester, and influences up to 5% of pregnant population . Maternal hyperglycemia may affect fetal development, especially cardiovascular system, and might lead to myocardial hypertrophy . Evaluation of fetal cardiac function in utero has always been a challenge.…”

“…Jin et al reported that the myocardium in the right ventricle and left atrium were significantly thicker than the control and also there was a reduction in glycogen content in cardiomyocytes. The high glucose also induced excess reactive oxygen species (ROS) production in the cardiomyocytes . These results suggest that GDM greatly influences the development of fetal heart.…”

Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies

“…However, the increased maternal blood glucose is considered the primary teratogenic agent in diabetic pregnancies. Previous studies in animal models have shown that even in the absence of DM, hyperglycemia alone can increase the risk of embryopathies [63,64]. Even a transient increase in glucose levels during early gestation (equivalent to the first eight weeks of gestation in humans), also known as the critical period of embryonic development, resulted in higher rates of congenital malformations in the offspring [65].…”