Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions

Abstract Intrauterine adhesions (IUAs) are a complex condition that frequently results in menstrual disturbances, infertility, and obstetric complications. Unfortunately, the underlying pathophysiology of IUAs remains poorly understood, and current treatments often exhibit limited efficacy. We perfo...

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Main Authors: Ping Li, Yu Jian, Xinyi Liu, Li Pan, Zhihui Tan, Nianchun Shan
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97433-1
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author Ping Li
Yu Jian
Xinyi Liu
Li Pan
Zhihui Tan
Nianchun Shan
author_facet Ping Li
Yu Jian
Xinyi Liu
Li Pan
Zhihui Tan
Nianchun Shan
author_sort Ping Li
collection DOAJ
description Abstract Intrauterine adhesions (IUAs) are a complex condition that frequently results in menstrual disturbances, infertility, and obstetric complications. Unfortunately, the underlying pathophysiology of IUAs remains poorly understood, and current treatments often exhibit limited efficacy. We performed the single-cell RNA-sequencing (scRNA-Seq) comparison of 5 endometrial tissues, including patients with confirmed intrauterine adhesions and healthy controls(HCs). We profiled the transcriptomes of 55,308 primary human endometrial cells isolated from healthy controls and intrauterine adhesions patients at single-cell resolution. Compared with those in HCs, the number of fibroblasts derived from IUAs significantly decreased. Further analysis found that fibroblasts subcluster 3 were enriched in the IUAs, whereas opposite in HCs. GO enrichment analysis revealed that specific genes of fibroblasts subcluster 3 were markedly involved in the positive regulation of embryonic placenta development, the response to reactive oxygen species and female pregnancy, and the positive regulation of the mitotic DNA damage checkpoint and DNA damage response. In addition, the proportion of proliferating endothelial cells was significantly lower in IUAs. GO enrichment analysis revealed that the specific genes were markedly involved in the positive regulation of cell cycle arrest, the cellular response to interferon − gamma and the negative regulation of the mitotic cell cycle. According to the number of intercellular receptor–ligand pairs, we identified endothelial cells as the core cell population. Our study provides deeper insights into the endometrial microenvironment disorders that are potentially applicable to improving therapeutics for IUAs.
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spelling doaj-art-8829779d14f849699d4e3bd7f251cc5b2025-08-20T02:10:53ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-97433-1Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesionsPing Li0Yu Jian1Xinyi Liu2Li Pan3Zhihui Tan4Nianchun Shan5Department of Obstetrics, Xiangya Hospital, Central South UniversityDepartment of Obstetrics, Xiangya Hospital, Central South UniversityDepartment of Gynecology, Xiangya Hospital, Central South UniversityDepartment of Gynecology, Xiangya Hospital, Central South UniversityDepartment of Gynecology, Xiangya Hospital, Central South UniversityDepartment of Gynecology, Xiangya Hospital, Central South UniversityAbstract Intrauterine adhesions (IUAs) are a complex condition that frequently results in menstrual disturbances, infertility, and obstetric complications. Unfortunately, the underlying pathophysiology of IUAs remains poorly understood, and current treatments often exhibit limited efficacy. We performed the single-cell RNA-sequencing (scRNA-Seq) comparison of 5 endometrial tissues, including patients with confirmed intrauterine adhesions and healthy controls(HCs). We profiled the transcriptomes of 55,308 primary human endometrial cells isolated from healthy controls and intrauterine adhesions patients at single-cell resolution. Compared with those in HCs, the number of fibroblasts derived from IUAs significantly decreased. Further analysis found that fibroblasts subcluster 3 were enriched in the IUAs, whereas opposite in HCs. GO enrichment analysis revealed that specific genes of fibroblasts subcluster 3 were markedly involved in the positive regulation of embryonic placenta development, the response to reactive oxygen species and female pregnancy, and the positive regulation of the mitotic DNA damage checkpoint and DNA damage response. In addition, the proportion of proliferating endothelial cells was significantly lower in IUAs. GO enrichment analysis revealed that the specific genes were markedly involved in the positive regulation of cell cycle arrest, the cellular response to interferon − gamma and the negative regulation of the mitotic cell cycle. According to the number of intercellular receptor–ligand pairs, we identified endothelial cells as the core cell population. Our study provides deeper insights into the endometrial microenvironment disorders that are potentially applicable to improving therapeutics for IUAs.https://doi.org/10.1038/s41598-025-97433-1Single cell RNA-sequencingIntrauterine adhesionsEndometrial cells
spellingShingle Ping Li
Yu Jian
Xinyi Liu
Li Pan
Zhihui Tan
Nianchun Shan
Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
Scientific Reports
Single cell RNA-sequencing
Intrauterine adhesions
Endometrial cells
title Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
title_full Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
title_fullStr Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
title_full_unstemmed Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
title_short Single-cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
title_sort single cell transcriptome profiling of the human endometrium of patients with intrauterine adhesions
topic Single cell RNA-sequencing
Intrauterine adhesions
Endometrial cells
url https://doi.org/10.1038/s41598-025-97433-1
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