Influence of gestational diabetes mellitus on vascular function in the placenta

Gestational diabetes mellitus (GDM) is associated with an increased risk for T2D and cardiovascular diseases in the mother and the child in later life. For the prevention of cardiovascular diseases, regulation of blood glucose is thought to be one of the key targets. One of the predominant causes of cardiovascular diseases arises from atherosclerotic changes in the vessel wall. The initial phase in the development of atherosclerosis is attributed to endothelial dysfunction and characterized by an imbalance between vasodilation and vasoconstriction, inhibition and promotion of proliferation and migration of smooth muscle cells, prevention and stimulation of monocyte adhesion to the vessel wall and aggregation of platelets. One of the most potent strategies to reduce cardiovascular mortality is frequent exercise. However, the impact of exercise during pregnancy on GDM-induced endothelial dysfunction of the offspring is not well-understood.

We hypothese that maternal gestational diabetes mellitus leads to a changed functional pattern in fetal endothelial cells and increasing risk of endothelial dysfunction in later life. We aim to gain new insights into the mechanisms involved in the development risk of endothelial dysfunction in fetuses exposed to GDM.

To investigate the impact of maternal GDM on fetal endothelial function and dysfunction, we intend to study vascular function in maternal uteropla-cental arteries of the placenta ex vivo in a small vessel myograph to determine endothelial dysfunction induced by gestational diabetes after childbirth.

Furthermore, comparative analyses of fetal gene expression profile of primary umbilical endothelial cells from infants of women with GDM and normoglycaemic controls will be performed. Expression including eNOS, adhesion molecules, markers for oxidative stress, inflammatory genes and glucose transporters are in major focus.

This project will allow novel insights into the underlying pathomechanisms of the increased risk for T2D and cardiovascular diseases in the mother and the child after gestational diabetes in later life.