Eide Irina P, Isaksen Christina V, Salvesen Kjell A, Langaas Mette, Günther Clara-Cecilie, Iversen Ann-Charlotte, Austgulen Rigmor
Department of Cancer Research and Molecular Medicine, DMF, Norwegian University of Science and Technology (NTNU), Medisinsk teknisk forskningssenter, Olav Kyrres gt. 3, N-7489 Trondheim, Norway.
J Reprod Immunol. 2007 Jun;74(1-2):7-14. doi: 10.1016/j.jri.2006.11.002. Epub 2006 Dec 28.
The Fas-Fas ligand (FasL) system contributes to immune tolerance at the feto-maternal site and has been ascribed a role in implantation and placental development by regulating trophoblast invasion and spiral artery remodelling. In the present study, we have examined FasL expression in decidual tissue from pregnancies with impaired placental development. Women with pre-eclampsia (PE) and/or fetal growth restriction (FGR) were enrolled as cases (n=33), and women with normal pregnancies were used as controls (n=27). Decidua basalis tissue was obtained by vacuum suction of the placental bed after delivery. FasL expression by extravillous trophoblasts (EVTs) and decidual cells (DeCs), together with EVT apoptosis, were assessed by immunohistochemistry. Levels of soluble FasL in maternal serum and apoptosis-related gene expression in decidual tissue were determined. The proportion of FasL-expressing DeCs was high in controls (72.0+/-10.2%), with a significant reduction among cases (58.1+/-19.7%; p=0.002), especially in those with FGR (54.3+/-19.9%; p<0.001). EVTs had a lower proportion of FasL expression than DeCs, with a less pronounced reduction in cases compared to controls (10.9+/-3.9 and 8.3+/-4.0%, respectively; p=0.02). Decidual FasL expression correlated with placental growth. The EVT apoptosis rate did not differ between cases and controls (1.1+/-1.9 and 1.1+/-1.3%, respectively). These findings indicate a reduction of immune privilege in decidua of PE/FGR pregnancies by reduced FasL expression and that DeCs may have a central role in the Fas-FasL-based feto-maternal immune balance.
Fas-Fas配体（FasL）系统有助于胎儿-母体部位的免疫耐受，并通过调节滋养层细胞侵袭和螺旋动脉重塑在着床和胎盘发育中发挥作用。在本研究中，我们检测了胎盘发育受损的妊娠蜕膜组织中FasL的表达。患有先兆子痫（PE）和/或胎儿生长受限（FGR）的女性被纳入病例组（n = 33），正常妊娠女性作为对照组（n = 27）。分娩后通过胎盘床真空吸引获取基蜕膜组织。通过免疫组织化学评估绒毛外滋养层细胞（EVT）和蜕膜细胞（DeC）的FasL表达以及EVT凋亡情况。测定母体血清中可溶性FasL水平和蜕膜组织中凋亡相关基因表达。对照组中表达FasL的DeC比例较高（72.0±10.2%），病例组显著降低（58.1±19.7%；p = 0.002），尤其是FGR患者（54.3±19.9%；p<0.001）。EVT的FasL表达比例低于DeC，病例组与对照组相比降低不明显（分别为10.9±3.9%和8.3±4.0%；p = 0.02）。蜕膜FasL表达与胎盘生长相关。病例组和对照组的EVT凋亡率无差异（分别为1.1±1.9%和1.1±1.3%）。这些发现表明，PE/FGR妊娠蜕膜中免疫特权因FasL表达降低而减少，并且DeC可能在基于Fas-FasL的胎儿-母体免疫平衡中起核心作用。
