在整个妊娠期，胎儿和母体细胞对重度子痫前期的空间分辨贡献

摘要(中文译文)

子痫前期的分子和细胞病理生理学仍然知之甚少，但越来越清楚的是，除了胎盘外，胎儿-母体界面的其他组织也会促进疾病的发展。在这里，我们通过跨越时间和空间询问与疾病相关的组织和细胞类型，区分胎儿和母体对重度子痫前期早期和晚期表现的贡献。考虑到妊娠晚期早产队列中的胎龄，我们发现胎盘中协同缺氧、血管生成失衡、纤维化和异常代谢的单细胞和空间分子特征。此外，我们报告了母体免疫特征，如线粒体功能障碍和干扰素信号传导延伸到子宫肌层和绒毛膜，可能导致母体全身炎症和内皮功能障碍，胎儿细胞与子宫肌层内皮细胞的相互作用受损是导致这一现象的原因。这些组织和细胞特异性反应是治疗的潜在靶点，在妊娠早期疾病中迅速考虑这些反应可能是有益的，因为其分子表现加重。因此，在妊娠期间及时干预可以改变重度子痫前期极其糟糕的预后。

Abstract

The molecular and cellular pathophysiology of preeclampsia remains poorly understood, but it is increasingly clear that in addition to the placenta, other tissues of the fetal-maternal interface advance the disease. Here, we distinguish fetal and maternal contributions to the early and late presentation of severe preeclampsia by interrogating, across time and space, tissues and cell types relevant to the disease. Accounting for gestational age in a third trimester preterm cohort, we find single-cell and spatial molecular signatures of concerted hypoxia, angiogenic imbalance, fibrosis, and aberrant metabolism in the placenta. In addition, we report maternal immune signatures such as mitochondrial dysfunction and interferon signaling extending to the myometrium and chorioamniotic membranes, likely contributing to the systemic inflammation and endothelial dysfunction in the mother, with impaired fetal cell interactions with endothelial cells in the myometrium contributing to it. These tissue- and cell-specific responses are potential targets for therapy, with their prompt consideration in early gestational disease likely beneficial because of its aggravated molecular presentation. Thus, timely intervention during gestation could change the extremely poor prognosis of severe preeclampsia.

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