Centre of Molecular Inflammation Research (CEMIR) and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR) and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Placenta. 2021 Feb;105:23-31. doi: 10.1016/j.placenta.2021.01.014. Epub 2021 Jan 20.
Inflammation is a normal physiological process that increases to harmful levels in preeclampsia. It affects the interaction between maternal immune cells and fetal trophoblasts at both sites of the maternal-fetal interface; decidua and placenta. The pattern recognition receptor nucleotide-binding oligomerization domain-containing protein (NOD)1 is expressed at both sites. This study aimed to characterize the cellular expression and functionality of NOD1 at the maternal-fetal interface of normal and preeclamptic pregnancies.
Women with normal or preeclamptic pregnancies delivered by caesarean section were included. Decidual (n = 90) and placental (n = 91) samples were analyzed for NOD1 expression by immunohistochemistry and an automated image-based quantification method. Decidual and placental explants were incubated with or without the NOD1-agonist iE-DAP and cytokine responses measured by ELISA.
NOD1 was markedly expressed by maternal cells in the decidua and by fetal trophoblasts in both decidua and placenta, with trophoblasts showing the highest NOD1 expression. Preeclampsia with normal fetal growth was associated with a trophoblast-dependent increase in decidual NOD1 expression density. Compared to normal pregnancies, preeclampsia demonstrated stronger correlation between decidual and placental NOD1 expression levels. Increased production of interleukin (IL)-6 or IL-8 after in vitro explant stimulation confirmed NOD1 functionality.
These findings suggest that NOD1 contributes to inflammation at the maternal-fetal interface in normal pregnancies and preeclampsia and indicate a role in direct maternal-fetal communication. The strong expression of NOD1 by all trophoblast types highlights the importance of combined assessment of decidua and placenta for overall understanding of pathophysiological processes at the maternal-fetal interface.
炎症是一种正常的生理过程，但在子痫前期会增加到有害水平。它会影响母体-胎儿界面的母体免疫细胞和胎儿滋养层之间的相互作用；蜕膜和胎盘。模式识别受体核苷酸结合寡聚化结构域蛋白（NOD）1 在这两个部位均有表达。本研究旨在描述正常和子痫前期妊娠母体-胎儿界面 NOD1 的细胞表达和功能。
剖宫产分娩的正常或子痫前期孕妇纳入研究。通过免疫组织化学和自动化基于图像的定量方法分析蜕膜（n=90）和胎盘（n=91）样本中 NOD1 的表达。用 NOD1 激动剂 iE-DAP 孵育蜕膜和胎盘外植体，并通过 ELISA 测量细胞因子反应。
NOD1 在蜕膜中的母体细胞和蜕膜和胎盘中的胎儿滋养层中均有明显表达，滋养层的 NOD1 表达密度最高。伴有正常胎儿生长的子痫前期与蜕膜中滋养层依赖性 NOD1 表达密度增加有关。与正常妊娠相比，子痫前期显示出蜕膜和胎盘 NOD1 表达水平之间更强的相关性。体外外植体刺激后白细胞介素（IL）-6 或 IL-8 的产生增加证实了 NOD1 的功能。
这些发现表明，NOD1 有助于正常妊娠和子痫前期母体-胎儿界面的炎症，并表明其在直接母体-胎儿通讯中起作用。所有滋养层类型均强烈表达 NOD1，突出了联合评估蜕膜和胎盘对全面了解母体-胎儿界面病理生理过程的重要性。
