Novel Insights into the Pathogenic Role of CSF1R in Endometriosis

Endometriosis (EM) is a prevalent gynecological disorder linked to pelvic pain, menstrual disturbances, and infertility. Despite its clinical burden, the molecular mechanisms underlying EM remain elusive, necessitating the discovery of novel biomarkers and therapeutic targets. This study explored the role of colony-stimulating factor 1 receptor (CSF1R) in EM through an integrative approach combining bioinformatics and experimental validation. Differentially expressed genes (DEGs) were identified from the GSE11691 dataset using the limma package. Weighted Gene Co-expression Network Analysis (WGCNA) identified disease-associated gene modules. A Protein-Protein Interaction (PPI) network was constructed, and candidate genes were selected using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms. Expression and function of CSF1R were validated in hEM15A cells via RT-qPCR, Western blotting, CCK-8, EdU, wound healing, and Transwell assays. WGCNA and PPI network analysis revealed a significant enrichment of genes within the PI3K/AKT/mTOR signaling pathway. Cross-validation using LASSO and Random Forest identified THBS2, CSF1R, IL-4R, and FLT1 as potential biomarkers. Among them, CSF1R was found to be significantly overexpressed in endometriotic stromal cells. Knockdown of CSF1R markedly suppressed cell proliferation, migration, and invasion, accompanied by decreased p-AKT expression. Rescue experiments using an AKT activator partially reversed these effects, supporting the functional role of CSF1R in modulating the AKT signaling pathway. CSF1R promotes the progression of endometriosis by modulating AKT signaling. It may serve as a valuable diagnostic biomarker and therapeutic target, providing new insights into endometriosis pathogenesis and treatment strategies. Similar content being viewed by others

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We thank the participants and medical staffs involved in the sample collection and experimental procedures. Special thanks to the laboratory team for their contributions to the data analysis and interpretation. Funding This work was supported by the Science and Technology Innovation Project of Shanghai Putuo District Health System (No. ptkwws202405). Author information Authors and Affiliations Contributions LY, JS and LZ conceived and designed research. CL and CC conducted experiments. QC and HZ contributed analytical tools. PD, XW and YH analyzed data. LY and JS wrote the manuscript. All authors read and approved the manuscript. Corresponding author Ethics declarations Ethical Approval This study was approve by the ethics committee of the Shanghai Putuo Maternity & Infant Health Hospital (PFYLL-2024001). Consent to Publish Written informed consent was obtained from all participants prior to their enrollment and sample collection, including explicit consent for publication. Conflict of Interest The authors declare no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Ye, L., Sun, J., Lu, C. et al. Novel Insights into the Pathogenic Role of CSF1R in Endometriosis. Reprod. Sci. (2026). https://doi.org/10.1007/s43032-026-02095-7 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s43032-026-02095-7