The pathological accumulation of EVTs within the trophoblast shell in preeclampsia revealed by spatial...

Preeclampsia (PE), a major unresolved public health issue, is characterized as a placenta-derived disorder. Impaired infiltration of extravillous trophoblasts (EVTs) from the trophoblast shell during early pregnancy is a key factor in the pathogenesis of PE. Thus, elucidating the molecular mechanisms underlying EVT dysfunction is of critical importance. In this study, spatial transcriptomics (ST) was employed to comparatively analyze placental tissues from PE and normal pregnancies. Compared with normal placentas, PE placentas exhibited significant attenuation of biological processes related to cell motility, invasion, and migration in the decidual region. Concurrently, multiple processes in the villus region of PE placentas, including tube development, regulation of cell population proliferation, regulation of cell differentiation, and vasculature development, showed marked downregulation. Among the 17 identified cell clusters, cluster 8, corresponding to the cytotrophoblast shell, displayed conspicuous accumulation of EVTs. Pseudotemporal trajectory analysis suggested that KRT8 is a key regulatory molecule in EVT differentiation. In summary, this study demonstrates that insufficient trophoblast invasion in the decidual region, poor vascular development in the villus region, and dysregulation of cell proliferation-differentiation collectively contribute to the occurrence of PE. Furthermore, the pathological aggregation of EVTs resulting from impaired invasion and migration of cells within the cytotrophoblast shell may be closely associated with the pathogenesis of PE, and KRT8 is likely to play a critical role in this process.