Vascular Biology of the Placenta

Abstract

The placenta is a gender-specific transitory organ with the sole purpose of enabling the growth and development of the fetus. It mediates the efficient transfer and exchange of nutrients and metabolites between maternal and fetal circulation, suppresses the mother’s immune response to the genetically distinct fetal “allograft,” and releases mediators that adapt the mother’s physiology to the specific requirements of pregnancy (1). The focus of this chapter is the vascular bed of the placenta. Establishment and maturation of the placental vascular bed require the functional integration of fetal and maternal circulations, coordination of maternal and fetal blood vessel formation, and involves unique processes of vascular remodeling. The blood-tissue interface in the placenta possesses characteristic features not found anywhere else in the body. It is genetically heterogeneous, involves both fetal and maternal blood vessels, and is formed by two different cell types, namely the endothelium and trophoblast. Due to their anatomical localization at the blood-tissue interface, trophoblast cells must acquire endothelial-like functions. This allows them to replace endothelium in the maternal arteries, and to increase blood flow to the placenta, and to participate in the regulation of hemostasis at the feto-maternal interface. Much of the interest in placental vascular biology has been fueled by the lack of knowledge about the pathogenesis of a single, but exceedingly common disease of pregnancy, pre-eclampsia (PE), which is caused by the dysfunction of the placental vascular bed. During mammalian embryogenesis, the vasculature of the placental yolk sac is the first fetal vascular bed to be established, and mutations that disrupt blood vessel formation and maturation in the yolk sac cause intrauterine death. The goals of this chapter are to: (1) provide an overview of placental development and anatomy of the placental vasculature; (2) review the unique aspects of the placental vasculature, i.e., the remodeling of spiral arteries, its functional specialization, and the adoption of an endothelial-like phenotype by trophoblast cells; (3) briefly discuss current hypotheses about the pathogenesis of PE; and (4) summarize the current knowledge about the striking importance of hemostasis for the development of the placental yolk sac vasculature.