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. 2025 Sep;42(9):3047-3064.
doi: 10.1007/s10815-025-03596-1. Epub 2025 Jul 24.

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

Jie Sheng  1   2 , Yanling Dong  3 , Yao Yuan  4 , Li Zhang  1 , Zhenpeng Sun  5 , Yan Huang  6 , Yingxiong Wang  7 , Siyu Lu  8
Affiliations

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

Jie Sheng et al. J Assist Reprod Genet. 2025 Sep.

Abstract

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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Bioinformatic analysis; Endometriosis; FXYD1; RSA; WGCNA.

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Conflict of interest statement

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.

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