Single-cell profiling of the microenvironment in decidual tissue from women with missed abortions

To define the decidual microenvironment in euploid and aneuploid misses abortions and elective termination of pregnancies.Prospective, multicenter, observational study.Tertiary hospital and descriptive analysis of transcriptomic data.A total of 34 patients experienced abortions, including 6 women who underwent elective terminations of pregnancy of unplanned pregnancies and 28 cases with missed abortions. All patients underwent their operations from Sep, 2021 to Sep, 2022.All women underwent villous copy number variation sequencing (CNV-Seq). Meanwhile, single-cell RNA sequencing (scRNA-Seq) were performed in the decidual tissues of 16 women, and Reverse transcription quantitative PCR (RT-qPCR) were performed in the decidual tissues of 18 women.ScRNA-Seq was used to explore the changes in the microenvironment of decidual tissues in abortions.scRNA-Seq indicated that the microenvironment of the decidual tissue of the missed-abortion group was altered, and that the stromal cells, NK cells, macrophages, and epithelial cells all reflected functional imbalances compared with the elective terminations of pregnancy group. We also noted a correlation between the proportion of senescent stromal cells and chromosomal abnormalities in missed-abortion embryos. The proportion of senescent decidual stromal cells in the decidual tissue of missed-abortion patients with common chromosomal abnormalities of the fetus was higher, and this was not conducive to fetal growth and was closely related to missed abortion. In addition, we ascertained that the strength of the HLA-KIR interaction between NK1 and NK2 subsets and non-senescent stromal cell subsets in the decidual tissue of missed abortions was weakened, potentially playing a role in the occurrence of missed abortion.The decidualization of stromal cells in the decidual tissue of missed abortions was impaired, the clearance of senescent stromal cells by NK cells was weakened, the killing toxicity of non-senescent stromal cells was enhanced, macrophages were insufficiently resident at the maternal-fetal interface, and epithelial cell differentiation was unbalanced-all creating a maternal microenvironment that was not conducive to fetal growth. We posit that interfering with the expression of dysregulated genes in the decidual tissue of missed abortions and reversing the maternal microenvironment might constitute an effective means toward improving the clinical outcome of missed abortions. Intriguingly, we observed a correlation between stromal cell senescence and embryonic chromosomal abnormalities. Thus, we hypothesize that the DIO2 marker of senescent stromal cells can be used as a risk indicator for the occurrence of missed miscarriages with chromosomal abnormalities of the embryos, and that it can be applied to guide the clinical diagnosis and treatment of recurrent abortion.