Single‐cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion

Objectives Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including recurrent spontaneous abortion (RSA). The role of cell heterogeneity of maternal decidua in RSA is yet to be illustrated. Materials and methods A total of 66,078 single cells from decidua samples isolated from patients with RSA and healthy controls were analysed by unbiased single‐cell RNA sequencing (scRNA‐seq). Results Our scRNA‐seq results revealed that stromal cells are the most abundant cell type in decidua during early pregnancy. RSA samples are accompanied by aberrant decidualization and obviously obstructed communication between stromal cells and other cell types, such as abnormal activation of macrophages and NK cells. In addition, the over‐activated TNF superfamily member 12 (TNFSF12, TWEAK) and FASLG in RSA are closely related to stromal cell demise and pregnancy failure. Conclusions Our research reveals that the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention. Recurrent spontaneous abortion (RSA), characterized by pregnancy loss before 20 weeks of gestation more than twice, is an intricated pregnancy complication with enigmatic underlying mechanism ascribes to its complex pathogenesis. The homeostasis between the developing foetus and maternal decidua is critical for pregnancy maintenance. By exploring the cell heterogeneity in normal and RSA decidua utilizing scRNA‐Seq, we unravel the discrepancies in cell composition and communications in these two distinct deciduae. Our investigations uncover that stromal cells are the most abundant cell populations in the decidua, with three different subpopulations at various decidualization stages and two fibroblasts. There are two separated trajectories of stromal cell decidualization marked by PLA2G2A and WNT4. As the most abundant cell population in the decidua, the stromal cells dominate the communications with other cell types, including endothelial cells, macrophages, uNK cells and perivascular cells. Compared with normal decidua, decidualized stromal cells are overtly decreased in RSA decidua with augmented macrophages. In addition, we present some previously unappreciated signaling pathways among different cells types in decidua and also depict the remarkably changed communica