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Regulation of vascular growth and function in the human placenta

Centre for Trophoblast Research and Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK¹ Centre for Trophoblast Research and Department of Obstetrics and Gynaecology, and the National Institute of Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, CB2 2SW, UK and² Academic Department of Obstetrics and Gynaecology, Institute for Women's Health, University College London, WC1E 6HX, London, UK

Correspondence should be addressed to G J Burton; Email: gjb2{at}cam.ac.uk

This paper is one of four papers that form part of a special Focus Issue section on Vascular Function in Female Reproduction. The Guest Editor for this section was H N Jabbour, Edinburgh, UK.

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.

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				H N Jabbour Vascular function in female reproduction Reproduction, December 1, 2009; 138(6): 867 - 868. [Full Text] [PDF]