Single-Cell RNA Sequencing deciphers the imbalance of Microenvironment of the Maternal-Fetal Interface in Cesarean Scar Pregnancy.

Cesarean scar pregnancy (CSP) has posed a serious threat to women's reproductive health. The view on its mechanism remained controversial. Here, we performed a single-cell sequencing on villi and decidua from three normal and three cesarean scar pregnancies in patients with a history of cesarean delivery. Enrichment analysis was performed to elucidate the functional roles of various cell types. Pseudotime analysis was utilized to infer the differentiation of trajectory. SCENIC provided insights into transcription regulation. CellChat was employed to explore intercellular interactions. A single-cell atlas of the maternal-fetal interface microenvironment in patients with a history of cesarean delivery was conducted to elucidate aberrant activities associated with CSP. Significant alterations were observed in trophoblast differentiation and function, including changes in angiogenesis, migration, and interactions with the extracellular matrix (ECM). A marked reduction in decidual stroma cells was observed, accompanied by abnormal ECM remodeling. Neutrophils (Neu) emerged as the principal immune cells, with elevated numbers and activation. Inflammatory pathways such as NF-κB in Neu increased. Cellular interactions between stroma cells and trophoblasts were mainly COLLAGEN, FN1, and LAMININ, and between immune cells and trophoblasts were VISFATIN and CXCL. This comprehensive single-cell analysis has elucidated the cellular heterogeneity at the maternal-fetal interface in patients with a history of cesarean delivery and shed light on distinct cellular abnormalities associated with CSP.