Placental vascular morphogenesis.

Appropriate growth and development of the placenta is essential for fetal growth and wellbeing, and indeed may be an important factor in determining adult health. As the fetus grows its demands increase and the capacity of the placenta to facilitate transfer between the fetal and maternal circulations increases as gestation progresses. The principal units for diffusional exchange of oxygen are the terminal villi, and these develop in the third trimester. It is thought that capillary growth within the villi drives the growth of these structures which are characterized by a high proportion of their volume being occupied by fetal capillaries and extreme thinning of the trophoblast and endothelial cell layers. In the first trimester the PO2 in the intervillous space is low and rises sharply at the start of the second. Endothelial growth is influenced by a variety of soluble factors, and several of these are regulated by oxygen, for example, vascular endothelial growth factor (VEGF), angiopoietin 2, and soluble flt (a VEGF antagonist). Thus, fetal demand may regulate villous growth and differentiation by altering local PO2 which, in turn, modulates growth factors (or their antagonists) to regulate endothelial growth and vessel re-modelling.