Quenby Siobhan, Mountfield Steve, Cartwright Judith E, Whitley Guy St J, Vince Gill
Department of Obstetrics and Gynaecology, University of Liverpool, Liverpool, United Kingdom.
Obstet Gynecol. 2004 Aug;104(2):354-61. doi: 10.1097/01.AOG.0000128902.84876.d4.
Unfractionated and low-molecular-weight heparin and low-dose aspirin are used for the prevention of pregnancy loss in pregnant women with thrombophilia. We investigated the effect of these drugs on in vitro models of human extravillous trophoblast motility and differentiation.
Chorion from term placentas was digested and extravillous trophoblast isolated. Extravillous trophoblast formed giant multinuclear cells that were counted after 24, 36, and 48 hours of culture. This model was then used to investigate the effect of unfractionated, low-molecular-weight heparin and aspirin on in vitro extravillous trophoblast differentiation at both therapeutic and supratherapeutic doses. In addition, the effect of unfractionated and low-molecular-weight heparin on hepatocyte growth factor-stimulated SGHPL-4 cell (extravillous trophoblast cell line) motility was determined by time-lapse microscopy.
At therapeutic doses unfractionated heparin promoted extravillous trophoblast differentiation. However, low-molecular-weight heparin inhibited giant multinuclear cells formation. At supratherapeutic doses, both low-molecular-weight and unfractionated heparin promoted extravillous trophoblast differentiation. Low-dose aspirin had minimal effects on the extravillous trophoblast differentiation. Both unfractionated and low-molecular-weight heparin inhibited hepatocyte growth factor-stimulated extravillous trophoblast motility at supratherapeutic doses. At a therapeutic dose of 0.25 IU/mL, only unfractionated heparin inhibited hepatocyte growth factor-stimulated motility, whereas low-molecular-weight heparin had no effect.
Our data suggest that unfractionated and low-molecular-weight heparin have differing effects on trophoblast differentiation and motility at therapeutic doses. This finding may be one of many factors that contribute to the clinical scenario.
普通肝素、低分子量肝素和小剂量阿司匹林用于预防患有血栓形成倾向的孕妇发生流产。我们研究了这些药物对人绒毛外滋养层细胞运动和分化的体外模型的影响。
消化足月胎盘的绒毛膜并分离出绒毛外滋养层细胞。绒毛外滋养层细胞形成巨大的多核细胞，在培养24、36和48小时后进行计数。然后使用该模型研究普通肝素、低分子量肝素和阿司匹林在治疗剂量和超治疗剂量下对体外绒毛外滋养层细胞分化的影响。此外，通过延时显微镜观察确定普通肝素和低分子量肝素对肝细胞生长因子刺激的SGHPL-4细胞（绒毛外滋养层细胞系）运动的影响。
在治疗剂量下，普通肝素促进绒毛外滋养层细胞分化。然而，低分子量肝素抑制巨大多核细胞的形成。在超治疗剂量下，低分子量肝素和普通肝素均促进绒毛外滋养层细胞分化。小剂量阿司匹林对绒毛外滋养层细胞分化的影响最小。在超治疗剂量下，普通肝素和低分子量肝素均抑制肝细胞生长因子刺激的绒毛外滋养层细胞运动。在0.25 IU/mL的治疗剂量下，只有普通肝素抑制肝细胞生长因子刺激的运动，而低分子量肝素没有作用。
我们的数据表明，普通肝素和低分子量肝素在治疗剂量下对滋养层细胞的分化和运动有不同的影响。这一发现可能是导致临床情况的众多因素之一。
