Trophoblast invasion in pre-eclampsia

It is generally accepted that insufficient invasion of trophoblast cells into the myometrial portions of the spiral arteries is thought to play a crucial role in the development of preeclampsia. As a consequence, uteroplacental vessels fail to undergo adaptive changes which are imperative to provide a sufficient blood supply to the placenta. Consecutive placental hypoxia is supposed to cause secretion/shedding of still unidentified placental metabolites resulting in different forms of pregnancy-induced hypertension. This review presents published data concerning the causes of insufficient trophoblast invasion in preeclampsia. Expression of HLA-G by extravillous trophoblast cells seems to be altered, resulting in activation of the maternal immune system. The pattern of integrin expression as well as the secretion of proteases is reported to be disturbed, which could lead to a reduced invasive potential of the trophoblast cells. Recent data indicate a pathophysiological role of NK-cells and macrophages in the altered trophoblast invasion. Also angiotensinogen Thr235 polymorphism seems to alter early physiologic changes in spiral arteries. In summary, preeclampsia seems to be induced by a multifactorial disturbance of trophoblast invasiveness which is characterized by reduced invasiveness of the trophoblast cells themselves and by an activated maternal immune response blocking the invasion by the semiallogenic trophoblast.