Factors regulating trophoblast migration and invasiveness: Possible derangements contributing to pre-eclampsia and fetal injury

Impaired trophoblast invasiveness and spiral arterial remodelling, which results in poor placental perfusion during early pregnancy, is believed to cause fetal injury and growth retardation, and also endothelial cell activation/dysfunction in a susceptible mother, leading to clinical manifestations of pre-eclampsia. This article briefly reviews the regulatory roles of certain locally active factors in trophoblast migration and invasiveness. This background is then used to discuss and debate whether derangements or dysfunction of some of these factors can manifest as early serum markers predictive of the disease, as opposed to the intermediate and late stage markers which may reflect manifestations and consequences of the disease. Of particular significance are the observed derangements in uPA/uPAR/PAI system, IGFBP-1, HGF, HB-EGF and TGFbeta, factors which are known to regulate trophoblast migration and invasiveness in situ. An emphasis is placed on the need for longitudinal studies in order to identify predictive serum markers which may help strategies for prevention or amelioration of fetal injury and pre-eclampsia. (C) 2003 Elsevier Science Ltd. All rights reserved.