Identification of shared pathogenetic mechanisms between endometriosis and RSA based on comprehensive bioinformatics analysis

Purpose Endometriosis (EM) and recurrent spontaneous abortion (RSA) exhibit clinical associations, yet their shared molecular mechanisms remain unclear. This study aimed to identify shared molecular mechanisms and potential hub genes underlying EM and RSA.

Differentially expressed genes (DEGs) were identified from EM (GSE7305) and RSA (GSE165004) datasets. Functional enrichment and weighted gene co-expression network analysis (WGCNA) revealed shared pathways and key modules. Venny software was used to identify hub genes between DEGs and key module genes. The diagnostic value of FXYD1 was assessed via ROC analysis. Regulatory networks and immune cell infiltration were explored. Pan-cancer analysis was conducted to assess FXYD1’s expression profile across tumor types. Single-cell RNA sequencing validated FXYD1 expression in EM tissues, maternal–fetal interface and RSA samples.

DEGs in EM and RSA were enriched in pathways associated with abnormal proliferation, immune dysfunction, and developmental regulation. FXYD1 was identified as a shared hub gene, upregulated in both conditions, with potential diagnostic value. It was correlated with immune cell populations, particularly natural killer (NK) cells. Pan-cancer analysis revealed widespread FXYD1 downregulation across multiple cancer types. Single-cell RNA sequencing confirmed elevated FXYD1 expression in stromal and decidual cells of RSA tissues, implicating its role in impaired decidualization.

FXYD1 emerges as a critical molecular link between EM and RSA, potentially contributing to decidualization dysfunction. Its dysregulation may underlie the shared pathophysiology of these conditions, offering new insights into their molecular mechanisms. Access this article We’re sorry, something doesn't seem to be working properly. Please try refreshing the page. If that doesn't work, please contact support so we can address the problem. Similar content being viewed by others Data availability All transcriptome data were obtained from publicly available datasets from ArrayExpress (https://www.ebi.ac.uk/arrayexpress/) and the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/), with detailed information provided in Supplementary Table S1.

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Author information Authors and Affiliations Contributions JS, SYL, and YXW conceived and designed the research. JS performed the bioinformatics analysis and drafted the manuscript. YLD and YH collected clinical samples. YY conducted RT-qPCR analysis. YY, LZ, and ZPS reviewed the manuscript. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Ethical approval The studies involving humans were approved by the Medical Ethics Committees of the Second Affiliated Hospital of Army Medical University (ID: 2024–311-02) and the First Affiliated Hospital of Chongqing Medical University (ID: 2023–075-02). The participants provided their written informed consent to participate in this study. Conflict of interest The authors declare no competing interests. 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 Sheng, J., Dong, Y., Yuan, Y. et al. Identification of shared pathogenetic mechanisms between endometriosis and RSA based on comprehensive bioinformatics analysis. J Assist Reprod Genet 42, 3047–3064 (2025). https://doi.org/10.1007/s10815-025-03596-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-025-03596-1