Abstract

Abstract Study question This study aimed to systematically understand the endometrial leukocyte types, inflammatory environment, and impaired receptivity at single-cell resolution. Summary answer These results provide new insights into the endometrial immune microenvironment and impaired endometrial receptivity in infertile women with minimal/mild endometriosis. What is known already Endometriosis is a common inflammatory disorder in women of reproductive age due to an abnormal endometrial immune environment and is associated with infertility. Study design, size, duration We profiled single-cell RNA transcriptomes of 138,057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. Participants/materials, setting, methods We profiled single-cell RNA transcriptomes of 138,057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. Main results and the role of chance We found that one cluster of epithelial cells that expressed PAEP and CXCL14 was mostly from the control during the window of implantation (WOI). This epithelial cell type is absent in the eutopic endometrium during the secretory phase. The proportion of endometrial immune cells decreased in the secretory phase in the control group, whereas the cycle variation of total immune cells, NK cells, and T cells was absent in endometriosis. Endometrial immune cells secreted more IL-10 in the secretory phase than in the proliferative phase in the control group; the opposite trend was observed in endometriosis. Proinflammatory cytokines levels in the endometrial immune cells were higher in endometriosis than in the control group. Trajectory analysis revealed that the secretory phase epithelial cells decreased in endometriosis. Ligand–receptor analysis revealed that 11 ligand-receptor pairs were upregulated between endometrial immune and epithelial cells during WOI. Limitations, reasons for caution Our study had some limitations, such as the small sample size and lack of validation experiments. Further studies are needed to demonstrated the conclusions of our bioinformatic analysis, like in situ validation of receptor-ligand pairs analysis. Therefore, more evidence is needed to clearly state the pathogenesis of endometriosis-associated infertility. Wider implications of the findings This database will provide an essential resource for understanding the eutopic endometrial inflammatory environment and defective endometrial receptivity in patients with endometriosis-associated infertility. Trial registration number 82071625

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