Novel Regulators of Hemodynamics in the Pregnant Uterus

The uterus is a highly dynamic organ, undergoing dramatic physiological changes during normal cyclicity and pregnancy. Many of these changes involve remodeling of the uterine vasculature in order to provide oxygen and nutrients to the developing embryo/fetus. Vasculogenesis, angiogenesis, vasodilation/vasoconstriction, and vascular permeability are coordinated by a vast network of autocrine, paracrine, and endocrine-signaling factors that derive from a number of cellular sources at the maternal:fetal interface, as well as from tissue outside the uterus. In this chapter, the dynamic changes that occur in uterine vasculature during pregnancy are described, and some of the hemodynamic regulatory factors are reviewed. These include uterine natural killer cells, sex steroid hormones, the calcitonin gene-related peptide family, angiopoietins, sphingolipids, and the renin-angiotensin system. Aberrancies in these factors are associated with disorders of uterine vascular remodeling, leading to conditions such as early pregnancy loss, preeclampsia, uterine hemorrhage, and intrauterine growth restriction. In addition, we introduce the role of the mas-related gene family in angiotensin signaling and endothelial function during pregnancy. Finally, this chapter introduces the novel concept that in addition to remodeling the vasculature to bring oxygenated maternal blood to the embryo, the gravid uterus synthesizes its own hemoglobin. Overall, this chapter provides an overview of the regulators of uterine vascular remodeling and hemodynamics during pregnancy and pregnancy-associated pathologies.