Reister Frank, Kingdom John C P, Ruck Peter, Marzusch Klaus, Heyl Wolfgang, Pauer Uli, Kaufmann Peter, Rath Werner, Huppertz Berthold
Department of Obstetrics and Gynecology, University Hospital Ulm, Ulm, Germany.
J Perinat Med. 2006;34(4):272-9. doi: 10.1515/JPM.2006.052.
Adaptation of uteroplacental arteries in patients with early-onset preeclampsia combined with IUGR is compromised due to insufficient invasion of extravillous trophoblast cells (EVT) into the spiral artery wall. The underlying molecular mechanisms are widely unknown. We investigated expression and possible mechanisms of regulation of different matrix-metalloproteases (MMPs) by EVT in placental bed biopsies from patients with early onset preeclampsia combined with IUGR and healthy pregnant women. Expression of MMP-3 and MMP-7 by EVT was markedly reduced in preeclamptic patients, especially close to spiral arteries. In contrast to healthy pregnancies these cells strongly expressed the receptor for leukemia inhibitory factor (LIF). LIF is known to suppress MMP-expression and is produced by uterine natural killer (uNK) cells which we found to be present in higher concentrations in the placental bed of preeclamptic patients, and accumulating aside the spiral arteries. We speculate that in preeclampsia a maternal immune cell network accumulating and interfering in the placental bed leads to an altered cytokine environment, resulting in disturbed trophoblast cell function such as impaired MMP expression and reduced invasiveness.
早发型子痫前期合并胎儿生长受限患者的子宫胎盘动脉适应性受损，原因是绒毛外滋养层细胞（EVT）对螺旋动脉壁的浸润不足。其潜在的分子机制尚不清楚。我们研究了早发型子痫前期合并胎儿生长受限患者及健康孕妇胎盘床活检组织中EVT对不同基质金属蛋白酶（MMPs）的表达及可能的调控机制。子痫前期患者中EVT的MMP - 3和MMP - 7表达明显降低，尤其是在螺旋动脉附近。与健康妊娠不同，这些细胞强烈表达白血病抑制因子（LIF）受体。已知LIF可抑制MMP表达，且由子宫自然杀伤（uNK）细胞产生，我们发现子痫前期患者胎盘床中uNK细胞浓度较高，并在螺旋动脉旁积聚。我们推测，子痫前期中母体免疫细胞网络在胎盘床积聚并产生干扰，导致细胞因子环境改变，进而致使滋养层细胞功能紊乱，如MMP表达受损和侵袭性降低。
