Academic Journal
Single-cell RNA sequencing reveals a pro-fibrotic epithelial subpopulation contributing to endometrial dysfunction in polycystic ovary syndrome.
| Title: | Single-cell RNA sequencing reveals a pro-fibrotic epithelial subpopulation contributing to endometrial dysfunction in polycystic ovary syndrome. |
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| Authors: | Wang Q; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Zhi Y; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Xie H; Reproductive Medicine Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Lang J; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Yang W; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Liang A; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Zhu X; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China., Fu Y; Center for Reproductive Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.; Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. |
| Source: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2026 Sep 03; Vol. 17, pp. 1873463. Date of Electronic Publication: 2026 Sep 03 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Polycystic Ovary Syndrome*/pathology , Polycystic Ovary Syndrome*/genetics , Polycystic Ovary Syndrome*/complications , Polycystic Ovary Syndrome*/metabolism , Endometrium*/pathology , Endometrium*/metabolism , Endometrium*/physiopathology , Epithelial Cells*/pathology , Epithelial Cells*/metabolism, Fibrosis/pathology ; Obesity/complications ; Obesity/pathology ; Obesity/genetics ; Obesity/metabolism ; Female ; Humans ; Adult ; Single-Cell Analysis ; Sequence Analysis, RNA ; Single-Cell Gene Expression Analysis ; Epithelial-Mesenchymal Transition ; Case-Control Studies |
| Abstract: | Background: Endometrial dysfunction in women with polycystic ovary syndrome (PCOS) significantly contributes to adverse pregnancy outcomes, including recurrent implantation failure and high miscarriage rates. However, the specific roles of individual cell types in this dysfunction, particularly in non-obese and obese PCOS patients, remain unclear. Methods: This study utilized single-cell RNA sequencing to comprehensively examine cellular heterogeneity in the proliferative-phase endometrium of non-obese PCOS, obese PCOS, and healthy controls. Results: Notably, we identified a distinct subpopulation of endometrial epithelial cells (EC) exhibiting a predisposition for epithelial-mesenchymal transition, characterized by elevated expression of decorin (DCN) and extracellular matrix 1 (ECM1) (DCNhighECM1high EC2). The proportion of these cells was significantly higher in PCOS patients, potentially disrupting normal epithelial function and reducing endometrial receptivity. Analysis of cell-cell communication revealed a notable decrease in anti-fibrotic bone morphogenetic protein (BMP) signaling in fibroblasts targeting DCNhighECM1high EC2, coupled with a marked increase in pro-fibrotic transforming growth factor beta (TGFβ) signaling in immune cells targeting DCNhighECM1high EC2. These changes were further enhanced in obese PCOS patients compared to non-obese PCOS patients. Conclusions: The imbalance between the BMP and TGFβ pathways likely drives the fibrotic transformation of endometrial epithelial cells in both non-obese and obese PCOS patients. Obese phenotype further exacerbates the fibrotic tendency, and compromises endometrial receptivity. Our findings highlight potential therapeutic targets for managing endometrial dysfunction in PCOS. (Copyright © 2026 Wang, Zhi, Xie, Lang, Yang, Liang, Zhu and Fu.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: endometrial dysfunction; epithelial cells; fibrosis; polycystic ovary syndrome; sc-RNA seq |
| Entry Date(s): | Date Created: 20260918 Date Completed: 20260918 Latest Revision: 20260919 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13581741 |
| DOI: | 10.3389/fendo.2026.1873463 |
| PMID: | 42755579 |
| Database: | MEDLINE |
| ISSN: | 1664-2392 |
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| DOI: | 10.3389/fendo.2026.1873463 |