Al-Nasiry S, Vercruysse L, Hanssens M, Luyten C, Pijnenborg R
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Placenta. 2009 Aug;30(8):719-25. doi: 10.1016/j.placenta.2009.05.006. Epub 2009 Jul 18.
During their invasion of the placental bed, interstitial trophoblasts fuse to multinuclear giant cells which are thought to have lost their invasive properties. Trophoblast fusion is associated with downregulation of E-cadherin, and persistent E-cadherin expression has been linked to defective placentation in preeclampsia. Since a previous study suggested 'premature' giant cell formation in preeclampsia, we started with the working hypotheses that fusion is increased in hypertensive pregnancies, and that the intensity of fusion correlates with the severity of disease. Using double immunostaining for E-cadherin and cytokeratin 7/17, nuclei in interstitially invasive trophoblasts (IT) in the myometrial compartment of the placental bed from normotensive pregnancies (NT, n=8), gestational hypertension (GH, n=4), preeclampsia (PE, n=9), and HELLP syndrome (n=5) were categorised according to the E-cadherin staining of the cell and their occurrence in single, clustered or multinuclear cells. GH and PE patients showed a higher percentage of nuclei in clustered non-fused E-cadherin-positive cells (P<0.01 and P<0.05), and in smaller (bi- and trinuclear) placental bed giant cells (P<0.05) compared to NT pregnancies, suggesting defective IT fusion. In contrast, in HELLP syndrome no such failed fusion could be discerned, which may support the idea of a heterogeneous aetiology of different hypertensive diseases of pregnancy. Since we are still ignorant about the specific role of mononuclear and multinuclear trophoblasts in the placental bed, it is not yet possible to relate the present findings to the pathogenesis of different categories of hypertensive pregnancies.
在侵入胎盘床的过程中，间质滋养层细胞融合形成多核巨细胞，这些细胞被认为已失去其侵袭特性。滋养层细胞融合与E-钙黏蛋白的下调有关，而E-钙黏蛋白的持续表达与子痫前期胎盘形成缺陷有关。由于先前的一项研究表明子痫前期存在“过早”的巨细胞形成，我们开始基于这样的工作假设：高血压妊娠中融合增加，且融合强度与疾病严重程度相关。使用针对E-钙黏蛋白和细胞角蛋白7/17的双重免疫染色，对正常血压妊娠（NT，n = 8）、妊娠期高血压（GH，n = 4）、子痫前期（PE，n = 9）和HELLP综合征（n = 5）的胎盘床肌层隔室中间质侵入性滋养层细胞（IT）的细胞核，根据细胞的E-钙黏蛋白染色及其在单核、聚集或多核细胞中的出现情况进行分类。与正常血压妊娠相比，GH和PE患者中聚集的未融合E-钙黏蛋白阳性细胞中的细胞核百分比更高（P < 0.01和P < 0.05），并且在较小的（双核和三核）胎盘床巨细胞中细胞核百分比更高（P < 0.05），提示IT融合存在缺陷。相比之下，在HELLP综合征中未发现这种融合失败的情况，这可能支持不同妊娠高血压疾病病因异质性的观点。由于我们仍不清楚单核和多核滋养层细胞在胎盘床中的具体作用，目前尚无法将本研究结果与不同类型高血压妊娠的发病机制联系起来。
