Regulation of vascular growth and function in the human placenta

Abstract

During the course of 9 months, the human placenta develops into a highly vascular organ. Vasculogenesis starts during the third week post-conception. Hemangioblastic cell cords differentiate in situ from mesenchymal cells in the villous cores, most probably under the influence of vascular endothelial growth factor (VEGFA) secreted by the overlying trophoblast. The cords elongate through proliferation and cell recruitment, and connect with the vasculature of the developing fetus. A feto-placental circulation starts around 8 weeks of gestation. Elongation of the capillaries outstrips that of the containing villi, leading to looping of the vessels. The obtrusion of both capillary loops and new sprouts results in the formation of terminal villi. Branching and non-branching angiogenesis therefore play key roles in villous morphogenesis throughout pregnancy. Maternal circulating levels of VEGFA and placental growth factor vary across normal pregnancy, and in complicated pregnancies. Determining the impact of these changes on placental angiogenesis is difficult, as the relationship between levels of factors in the maternal circulation and their effects on fetal vessels within the placenta remains unclear. Furthermore, the trophoblast secretes large quantities of soluble receptors capable of binding both growth factors, influencing their bioavailability. Villous endothelial cells are prone to oxidative stress, which activates the apoptotic cascade. Oxidative stress associated with onset of the maternal circulation, and with incomplete conversion of the spiral arteries in pathological pregnancies, plays an important role in sculpting the villous tree. Suppression of placental angiogenesis results in impoverished development of the placenta, leading ultimately to fetal growth restriction. Reproduction (2009) 138 895-902

The placenta: a multifaceted, transient organ

“…Vasculogenesis starts with the differentiation in situ of haemangioblastic clusters within the mesenchymal core of early villi during the third week post-fertilization [57]. The clusters form cords of cells, usually located immediately beneath the trophoblastic basement membrane.…”

“…These are not displaced until onset of the fetal placental circulation towards the end of the first trimester. The villous capillary network undergoes continued sprouting and remodelling throughout gestation [60], regulated most likely by angiogenic factors in response to changes in oxygen tension and mechanical stimuli such as shear stress and cyclic strain [57].…”

Impact de l’obésité et du diabète maternels sur la fonction placentaire

“…Les taux de leptine et de cytokines proinflammatoires comme le TNF-, l'IL-6 et l'IL-1 sont également augmentés. Ces cytokines participent à la physiopathologie de cette maladie de même que le stress oxydatif qui, par son rôle d'inducteur de l'apoptose des anomalies suggérant des altérations de la vascularisation placentaire touchant l'expression de facteurs proangiogéniques comme le VEGF (vascular endothelial growth factor) et de ses récepteurs ont d'ailleurs été observées dans les placentas de femmes obèses [14]. Des perturbations du développement vasculaire placentaire [15] mais aussi des réductions des flux sanguins utérins [10] ont été décrites dans des modèles animaux d'obésité au cours de la gestation (Tableau I).…”

Evaluation of Placental Blood Flow in Patients with Placental Insufficiency

“…Those problems in early pregnancy may affect chorionic villi, leading to retroplacental or subchorionic hematomas and spontaneous abortion. [4,5] Placental insufficiency is a major problem of modern obstetrics due to its link to maternal and perinatal morbidity and mortality. [1,2] Placental insufficiency is classified according to the period of its onset (primary placental insufficiency, arising before 16 weeks of gestation, and secondary, arising after 16 weeks of gestation).…”