Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)^1,2,3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal–fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.

从妊娠早期开始，胎儿来源的绒毛外滋养细胞 (EVT) 侵入子宫并重塑其螺旋动脉，将其转变为大而扩张的血管。已经提出了几种机制来解释 EVT 如何与母体蜕膜协调以促进有利于螺旋动脉重塑 (SAR) 的组织微环境^1,2,3 。然而，关于哪些免疫细胞和基质细胞参与这些相互作用以及这种相互作用如何随胎龄变化仍然存在争议。在这里，我们使用多组学方法，结合空间蛋白质组学和转录组学的优势，构建了妊娠前半期人类母胎界面的时空图谱。我们使用飞行时间多重离子束成像和 37 重抗体组来分析 66 名妊娠 6 至 20 周个体的完整蜕膜内的约 500,000 个细胞和 588 个动脉，并将该数据集与共同注册的转录组学概况相结合。孕龄显着影响母体免疫和基质细胞的频率，表达 CD206、CD163、TIM-3、galectin-9 和 IDO-1 的耐受亚群在以后的时间点变得越来越丰富和共定位。相比之下，SAR 进展优先与 EVT 侵袭相关，并由 78 个基因本体通路转录定义，表现出明显的单相和双相趋势。最后，我们开发了一个 SAR 综合模型，其中侵袭伴随着促血管生成、免疫调节 EVT 程序的上调，这些程序促进与血管内皮的相互作用，同时避免母体免疫细胞的激活。