Angiogenic Growth Factor Expression in Placenta S.K. Smith, Y. He, D.E. Clark, and D.S. Charnock-Jones New blood vessel growth is generally a rare event in the healthy adult. However, a notable exception to this is the female reproductive tract where cyclic angiogenesis occurs. Striking new vessel growth and remodeling also occurs during placentation; thus angiogenesis is essential for reproductive success. Vascular endothelial growth factor is a potent stimulator of this process and its production and action is tightly regulated. Indeed the placenta is a rich source of a soluble variant of the fit-1 receptor which seems to protect the placenta from the effects of excess vascular endothelial growth factor. The balance between new vessel growth (in the placental villi for example) and endothelial cell loss in the spiral arteries within the decidua is a delicate one. This is influenced by the local production of promotors and inhibitors of endothelial cell activation. Perturbation of this may lead to maternal pathology during pregnancy. Copyright 9 2000 by W.B. Saunders Company ff 'n eutherian mammals, the placenta services to facilitate the transport of nutrients from the maternal circulation and for the removal of metabolic waist products in the opposite direc- tion. The anatomy of such structures may vary but the basic structure always consists of a min- imum of one epithelial (trophoblast) and one endothelial cell layer that separates the fetal and maternal circulation, a In humans the primitive trophectoderm develops into two structures. First, extravillous trophoblast derived from cy- totrophoblast migrates into the decidua and es- tablishes the anchoring villi. These structures do not permit the transport of nutrients di- rectly into the placenta. Rather their function is to secure the placenta to the maternal de- cidua. However, their additional function is of great importance as they are required for the adaptation of the maternal circulation that transforms the high resistance low capacitance non-pregnant spiral arterioles to the low resis- tance high capacity vessels that supply the la- cunae into which the fetal villous trophoblast projects. The successful establishment of pregnancy thus requires two specific events of vascular re- From the Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Cambridge, UK. Address reprint requests to S.K. Smith, MBBS, MD, Department o[ Obstetrics & Gynaecology, The Rosie Hospital, Robinson Way, Cambridge CB2 2SW, UK. Copyrigt,t 9 2000 by W.B. Saunders Company O146-0005/00/2401-002051 O. 00/0 modelling to occur, that in the mother and that of the fetal placental circulation. The develop- ment of the fetal villi is determined by the un- derlying vascular development. Branching of the capillaries inducing branching of the villi. In both events angiogenesis, the development of blood vessels from pre-existing vessels deter- mines the successful outcome of the entire pro- tess. 2 The regulation of angiogenesis is complex and involves the interaction of inhibitory and stimulatory factors. 3 One of the families of genes responsible for the stimulation of angio- genesis is the VEGF gene family. This article documents the expression of these genes in the placenta and placental bed and investi- gates the possibility that abnormal expression of the growth factors or their receptors may be responsible for the maternal syndrome of pre- eclampsia. The VEGF Gene Family The prototype of this family is VEGF-A, a hepa- rin, homodimeric glycoprotein of 30-46 kd. 4 The protein is derived from eight exons and at least five splice variants of 121,145, 165, 189, and 205 amino acids have been identified. Four further VEGFs-B, 5 C, 6 D 7 and E have been identified and also PLGF. s,~ VEGF-A binds two receptors, fit-1 and KDR (VEGFR-1 and VEGFR-2). The binding of 82 Seminars in Perinatology, Vol 24, No 1 (February), 2000: pp 82-86