Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE). Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE. In contrast to published literature, we demonstrate that placenta-associated diamine oxidase (DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels. Cultures of primary EVTs express and secret large amounts of bioactive DAO. ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs. Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels. This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.

中文翻译：

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妊娠相关的二胺氧化酶起源于绒毛外滋养细胞，在先兆子痫前期减少。

人绒毛外滋养层细胞（EVT）侵入怀孕子宫是建立母胎界面的关键事件。在动脉重构不足中表现出的EVT功能受损与严重的妊娠疾病早发先兆子痫（eoPE）有关。最近的研究表明，EVT在妊娠的头三个月侵入整个子宫血管，包括动脉，静脉和淋巴管。因此，我们假设EVT衍生因子在妊娠早期孕妇的血液循环中积累，可能有助于预测eoPE。与已发表的文献相反，我们证明胎盘相关的二胺氧化酶（DAO）不是由母体蜕膜细胞表达的，而是由EVT单独表达的，尤其是在接近蜕膜血管的情况下。初级EVT的培养物表达并分泌大量具有生物活性的DAO。ELISA测量表明，孕周（GW）7前后孕妇DAO血浆水平出现了妊娠特异性升高，这与EVT的血管浸润相吻合。令人惊讶的是，eoPE病例的DAO水平与怀孕前三个月的对照组相比明显降低（40％），但在妊娠中期没有发现差异。此外，含有DAO的怀孕血浆会迅速使病理生理相关的组胺水平失活。这项研究代表了第一个概念证明，提出了EVT特有的特征作为eoPE预测的诊断目标。与妊娠早期相比，eoPE患者的DAO水平明显低于对照组（40％），但在妊娠中期没有差异。此外，含有DAO的怀孕血浆会迅速使病理生理相关的组胺水平失活。这项研究代表了第一个概念证明，提出了EVT特有的特征作为eoPE预测的诊断目标。与妊娠早期相比，eoPE患者的DAO水平明显低于对照组（40％），但在妊娠中期没有差异。此外，含有DAO的怀孕血浆会迅速使病理生理相关的组胺水平失活。这项研究代表了第一个概念证明，提出了EVT特有的特征作为eoPE预测的诊断目标。