Insights into the maternal-fetal interface from spatial multi-omics.

Recent advances in spatial transcriptomics, spatial proteomics, spatial metabolomics, and multimodal integration strategies have substantially transformed current understanding of the maternal-fetal interface. Rather than functioning as a uniform tissue, the placenta is increasingly recognized as a highly organized multicellular ecosystem in which trophoblast, immune, vascular, and metabolic compartments establish spatially coordinated microenvironments that regulate trophoblast differentiation, immune adaptation, vascular remodeling, and placental homeostasis. Emerging evidence further suggests that placental disorders are driven not simply by trophoblast-intrinsic abnormalities but by dysregulation of localized microenvironmental niches within placental tissues. In particular, preeclampsia (PE) and placenta accreta spectrum (PAS) appear to represent opposite spatial ecosystem states characterized by invasion-restrictive versus invasion-permissive microenvironments, respectively. In this review, we summarize recent spatial multiomic studies focused on the maternal-fetal interface and discuss how spatially resolved approaches are reshaping current understanding of placental disease through a spatial microenvironmental framework.