The single-cell atlas of the murine reproductive tissues during preterm labor

Abstract

Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the multi-etiological syndrome of preterm labor. Intra-amniotic infection is the best-established causal link to preterm labor and birth, and involves the premature activation of the parturition cascade in the reproductive tissues (uterus, decidua, and cervix). However, the simultaneous investigation of the cellular landscape and interaction networks in such tissues at single-cell resolution had not been undertaken. Herein, we utilized scRNA-seq to reveal that preterm labor affects the cellularity of the uterus, decidua, and cervix through immune cell infiltration and altered transcriptomic profiles of non-immune cell types. Preterm labor-affected cells showed shared and distinct immune processes, the latter indicating tissue-specific cellular functions. Cell-cell communication analysis implicated immune and non-immune cell types in preterm labor-associated inflammatory pathways across tissues. Next, correlation between uterine transcriptomic data from mice with local or systemic inflammation-induced preterm labor indicated significant overlap in labor-associated gene expression. Last, comparison of cell-cell communication in the murine and human uterus revealed shared signaling pathways implicated in preterm and term parturition. Together, these findings provide novel insight into the cellular landscape, dynamics, and communications in the reproductive tissues during preterm labor leading to premature birth.

Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

“…After stringent quality control filters (see Methods), we recovered 26,493 high-quality cells across the six time points. Epithelial cells were the main cell type recovered at each time point while the number of stromal cells captured was low relative to their abundance in tissue ( Fig 2A ), as observed in another study (Garcia-Flores et al, 2022). Clustering of all time points showed five distinct cell types that were captured from the cervical tissue: epithelial (Epcam + , Ehf + ), immune (Tyrobp + ), endothelial (Pecam1 + ), stromal (Col1a2 + ), and red blood cells (Hbb-bt + ) ( Fig 2B and C ) (Becht et al, 2018).…”

Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

“…The dominance of epithelia in single-cell libraries is also observed in another study. 39 Clustering of all time points showed five distinct cell types that were captured from the cervical tissue: epithelial (Epcam + , Ehf + ), immune (Tyrobp + ), endothelial (Pecam1 + ), stromal (Col1a2 + ), and red blood cells (Hbb-bt + ) ( Figures 2 B and 2C). 40 The expression of additional cell type-specific genes also confirms the identification of the cell types ( Figure 2 D).…”