Single-cell analysis reveals the diversity of human fetal membrane and adjacent placental cells with preterm premature rupture of membranes.

The occurrence of preterm premature rupture of membranes (PPROM) significantly impacts maternal and fetal health due to its association with the cellular composition and genetic changes of the fetal membrane. However, the specific cell type responsible for triggering PPROM and the underlying mechanisms are still largely unexplored. We employed single-cell RNA sequencing (scRNA-seq) analysis on fetal membrane along with adjacent placental tissues about two centimeters from the umbilical cord obtained from women who delivered full-term in labor (FTIL), preterm premature without rupture of membrane (PPWROM), as well as PPROM，immunofluorescence were used to verify the findings. Our result s highlighted notable differences in cell type composition and interactions among these three groups. Of particular significance, we have identified a previously unrecognized subtype of trophoblast cells known as FABP7+Tb, a transitional state cell between cytotrophoblasts (CTB) and extravillous trophoblasts (EVT) cells, which appears to have some impact on PPWROM. Additionally, up-regulated expression of MMP11 in EVT-1 may serve as a promising biomarker for PPROM diagnosis. Furthermore, our study unveiled distinct interaction patterns among different trophoblast subtypes under varying pathological conditions, as well as significant variations in the interactions of trophoblast cells with other cell types, especially the pathways that are orchestrated by cell-cell cross-talk. Our study offers a comprehensive cell type and interaction map for the human fetal membrane along with adjacent placental tissues about two centimeters from the umbilical cord, providing insights into the molecular mechanisms that drive PPROM and uncovering potential targets for the early prediction of this condition.