Grant: CIHR New Investigator

The movement of blood containing oxygen and nutrients from the mother to the fetus is important for proper fetal growth. Blood from the mother flows to the uterus and placenta to reach the fetus. If this blood flow is decreased, the growth of the fetus is reduced. Growth restricted newborns suffer many adverse consequences and are also at increased risk for cardiovascular disease when they become adults. Blood flow is controlled by changes to the diameter of arteries (vascular tone) through constriction or relaxation. Arteries contain endothelial cells which are surrounded by the smooth muscle cells. One factor that can act on both cell types is a lipid called sphingosine 1-phosphate (S1P). This lipid causes relaxation or constriction depending on whether it binds to receptors on the endothelial or smooth muscle cells, respectively. This study looks at a novel role for S1P in vascular tone regulation of arteries that are important for blood flow to the fetus: uterine and placental arteries. Understanding these responses in normal pregnancy will help to develop methods to prevent or treat fetal growth restriction. Our hypothesis is that when S1P binds to receptors on the endothelial cells, there will be increased relaxation of uterine arteries in pregnancy which will be lost in pregnancies with growth restricted babies. This relaxation is important because it provides a balance for constriction by S1P and other factors. This balance is what maintains the blood flow from mother to fetus. We will use two approaches to examine this question: 1) We will compare the response to S1P in uterine arteries from pregnant and non-pregnant mice; 2) We will also use arteries from human placentas of normal babies and compare their response to S1P to that from growth restricted babies. We predict that the increased relaxation response to S1P in normal pregnancy will be lost in growth restricted pregnancies.