Villous sprouting: fundamental mechanisms of human placental development

There is increasing evidence that maldevelopment of the placental villous t ree can play an important role in the pathogenesis of various pregnancy dis eases. In this review we present the most recent advances of cellular and m olecular mechanisms involved in the early formation of chorionic villi, In particular we focus our attention on the structural events during early vil lous sprouting leading to the formation of the mesenchymal villi which are the forerunners of all other villous types, i.e. immature intermediate vill i, stem villi, mature intermediate villi and terminal villi, Early villous sprouting starts as 'hot spots) which are circumscribed areas consisting of highly proliferating cytotrophoblastic and stromal cells. The post-prolife rative cytotrophoblastic cells fuse with the overlying syncytium leading to the formation of the trophoblastic sprouts. When villous mesenchyme invade s the trophoblastic sprouts, the latter are transformed into villous sprout s. The vascularization of the villous sprouts leads to the formation of the mesenchymal villi, the most basic villous type. This process is repeated t hroughout pregnancy. We analyse the influence of various extracellular matr ix molecules, e.g. tenascin and hyaluronic acid, on the formation of hot sp ots and mesenchymal villi as well as the transformation of the latter in ot her villous types. We present a critical survey on the data on vessel forma tion related to villous sprouting and morphogenesis of mesenchymal villi as well as the expression of various angiogenic factors and their receptors.