Not trophoblast alone: a review of the contribution of the fetal microvasculature to transplacental exchange.

The fetal microcirculation of the term human placenta offers an interesting microvascular model. A perfused placenta can be used for integrated studies of vascular permeability-structure relationships. The organization of the paracellular pathway in human placental microvessels closely resembles not only that of the guinea-pig placenta, but also that seen in typical continuous non-cerebral capillaries such as those of the myocardium. This uniformity of organization has allowed the development of a model of the organization of endothelial junctional complexes that allows testable predictions about the relationship between junctional organization and microvascular permeability. The key features of this model are: (1) molecular size restriction may be determined by a fibre matrix based on cadherin arrays in the zonula adhaerens. (2) The zonula occludens (tight junction) is discontinuous and so cannot act as a molecular sieve for solutes. It may serve as a shutter that limits the proportion of the paracellular cleft available for permeation. The main implication for placental function is that the human placental microcirculation is relatively tight and is an important restriction to diffusive permeation of the maternal-fetal barrier by large molecules.