Expression and function of placenta growth factor: implications for abnormal placentation

OBJECTIVE: Essential requirements for successful gestation include the coordinated growth and differentiation of the placenta and the development of a functional placental vasculature. However, relatively little is known about factors that are responsible for regulating these functions. One angiogenic growth factor that might be involved in regulating both vascular endothelial cell and trophoblast function is placental growth factor (PGF). METHODS: Current published reports were surveyed and our own work was reviewed to highlight the expression, function, and potential significance of PGF at the human maternal-fetal interface. RESULTS: PGF is highly expressed in trophoblasts during normal pregnancy, and its expression is significantly decreased in preeclampsia, an obstetric complication presumed to be associated with placental bed hypoxia and ischemia. In agreement with this, in vitro trophoblast expression of PGF can be down-regulated by low oxygen tension. The cognate receptor for PGF, fms-like tyrosine kinase receptor, is expressed on trophoblasts as well as vascular endothelial cells, suggesting that it has autocrine and paracrine functions. Accordingly, PGF can regulate proliferation in first trimester trophoblasts, apoptosis in term trophoblasts, and it can directly or indirectly regulate vascular growth, maturation, and permeability. CONCLUSIONS: Many obstetric complications, most notably preeclampsia, are associated with aberrant trophoblast function and inadequate or dysfunctional vasculature within the developing placenta. The ability of PGF to influence trophoblast and vascular endothelial cells provides clear impetus for further studies to investigate the biological and clinical significance of PGF in normal and abnormal human pregnancies.