Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies.

Patterns of fetoplacental angiogenesis vary not only during the course of a normal pregnancy but also in certain pregnancy pathologies. Here, we review some of the molecular and morphological events which occur in complicated pregnancies. The pregnancy complications are chosen in an attempt to represent the possible different origins (preplacental, uteroplacental, postplacental) of fetal hypoxia. Molecular events focus on reported changes in hypoxia-inducible factors, angiopoietins and the vascular endothelial, basic fibroblast and placenta growth factors and their receptors. Morphological changes focus on patterns of angiogenesis (branching and non-branching) and a consistent set of morphometric descriptors (covering measures of total capillary growth, villous capillarization and capillary size and shape in transverse section). Apart from some uncertainties due to lack of information, or failure to resolve fully the effects of intrauterine growth restriction and pre-eclampsia, alterations in the angiogenic growth factors and morphologies of capillaries and villi in different complicated pregnancies seem to conform reasonably well to those predicted by the fetal hypoxia paradigm. However, it is clear that future studies on the effects of different origins of fetal hypoxia should exercise more care in the choice and interpretation of relevant descriptors and take more account of the parallel effects of possible confounders. In addition, rather than comparing uncomplicated and complicated pregnancies only at term, more information about molecular and morphological events that occur throughout gestation would be extremely valuable. This includes further studies on changes in growth factor receptors, the less-well-documented angiogenic factors (e.g. angiogenin, angiostatin, endostatin) and the associations between endothelial cells and pericytes. A more integrated approach involving also parallel analysis of the effects of erythropoietin and other potential vasoactive factors on the behaviour and morphology of fetal vessels would be beneficial.