Development of the placental villous tree and its consequences for fetal growth

Co-ordinated development of the fetal villous tree of the placenta is neces sary :for continued fetal growth and well-being. Before fetal viability, bl ood vessel development within the developing immature intermediate villi (I IV) is characterized by branching angiogenesis, such that the placenta expa nds to produce 10-16 generations of stem villi. Once fet;al viability is at tained, a developmental switch occurs to form large numbers of gas-exchangi ng terminal villi (TV) by non-branching angiogenesis in mature intermediate villi (MIV). Several growth factors, including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), angiopoietins, and angiostat ins are produced within the villi and act locally, via their receptors, to control angiogenesis. Their relative contributions to placental vascular ( development are not fully understood at the present time. Severe early-onse t intrauterine growth restriction (IUGR) is characterized by absent/reverse d end-diastolic flow velocity (ARED) in the umbilical arteries, leading to fetal hypoxia, acidosis and a substantial rise in perinatal mortality and m orbidity. The placentas from such cases show a deficit in peripheral villou s development, which may be perpetuated by the effects of oxygen (delivered by maternal blood into the intervillous space) upon VEGF-directed angiogen esis, the so-called 'placental hyperoxia' theory of villous maldevelopment. Trophoblast apoptosis is a significant feature of early-onset IUGR and may explain poor flow-independent transfer of nutrients to the fetus. Finally, since transgenic mouse studies highlight the importance of trophoblast-der ived transcription factors for placental villous (labyrinth) development, i t is possible that the villous trophoblast controls the orderly development of the underlying mesoderm and blood vessels into the fetal villi. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.