Department of Perinatal Medicine, Pregnancy Research Centre, The Royal Women's Hospital, Parkville, Australia.
Am J Pathol. 2012 Feb;180(2):693-702. doi: 10.1016/j.ajpath.2011.10.023. Epub 2011 Dec 2.
Pregnancy represents a hypercoagulable state characterized by increased thrombin generation. However, placentas from fetal growth restriction (FGR) pregnancies are characterized by increased fibrin deposition and thrombi in the vasculature, indicative of a further increase in thrombin activation and a disturbance in coagulation in this clinical setting. The cause of the coagulation disturbance observed in FGR pregnancies is currently unknown. Anticoagulant mechanisms are crucial in the regulation of thrombin activity, and current evidence suggests that syndecans are the principal placental anticoagulant proteoglycans. The aim of this study was to determine the localization, distribution, and expression of syndecans 1 to 4 in placentas complicated by idiopathic FGR compared with gestation-matched controls. Immunohistochemistry results revealed that all of the syndecans were localized to cells located closely to the maternal and fetal circulation. The mRNA and protein expression levels of both syndecan 1 and syndecan 2 were significantly decreased in FGR samples compared with controls. This is the first study to demonstrate the differential expression of syndecans 1 to 4 in idiopathic FGR placentas compared with controls. Reduced levels of syndecan expression may result in increased placental thrombosis in the uteroplacental circulation and may therefore contribute to the pathogenesis of FGR.
妊娠表现为一种高凝状态，其特征是凝血酶生成增加。然而，胎儿生长受限（FGR）妊娠的胎盘表现为血管内纤维蛋白沉积和血栓增加，表明在此临床环境下凝血酶激活进一步增加，凝血受到干扰。目前尚不清楚 FGR 妊娠中观察到的凝血紊乱的原因。抗凝机制是调节凝血酶活性的关键，目前的证据表明，连接蛋白是主要的胎盘抗凝蛋白聚糖。本研究旨在确定与胎龄匹配的对照组相比，特发性 FGR 胎盘组织中连接蛋白 1 至 4 的定位、分布和表达。免疫组织化学结果表明，所有连接蛋白均定位于与母体和胎儿循环紧密相邻的细胞中。与对照组相比，FGR 样本中 syndecan 1 和 syndecan 2 的 mRNA 和蛋白表达水平均显著降低。这是首次研究表明，与对照组相比，特发性 FGR 胎盘组织中连接蛋白 1 至 4 的表达存在差异。连接蛋白表达水平降低可能导致胎盘血管内血栓形成增加，从而可能导致 FGR 的发病机制。
