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MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis

Genes & Immunity (2026)Cite this article

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Abstract

Abnormal accumulation of prostaglandin E2 (PGE2) is a secondary effect of the presence of bacterial infection, and usually causes overproduction of proinflammatory cytokines, thereby leading to infiltration of neutrophils, serving as a key etiology of endometritis linking to infertility. Metastasis-associated protein 1 (MTA1), functioning as a master transcriptional coregulator, is increasingly recognized as an important influencer of inflammation, but its functional roles in endometritis, if any, remain unexplored. Herein, by investigating clinical correlations, in vitro assays, and uterus-specific Mta1 knockouts, we show that MTA1 expression was significantly downregulated in endometrial biopsies from patients with chronic endometritis (CE) and in human endometrial stromal cells (HESCs) challenged with clinically relevant pathogenic dosage of lipopolysaccharide (LPS). MTA1 deletion augmented endometrial neutrophil infiltration, exacerbated inflammatory phenotype and negatively affected the outcome of LPS-induced endometritis through modulation of PGE2 secretion. We have also identified cyclooxygenase-2 (COX2) as the key rate-limiting enzyme responsible for the deregulated PGE2 synthesis in MTA1 deficiency-exacerbated endometritis. Mechanistically, MTA1 negatively regulated the transcription of Cox2, likely in collaboration with HDAC2 (histone deacetylase 2), in LPS-challenged endometrial stromal cells (ESCs). In summary, MTA1 signaling may govern appropriate inflammatory response in ESCs against the pathogenesis of endometritis.

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Fig. 1: Overview of the study design.
Fig. 2: MTA1 signaling is deactivated in ESCs associated with human chronic endometritis.
Fig. 3: Genetic deletion of Mta1 enhances endometrial neutrophil infiltration in LPS-induced endometritis.
Fig. 4: The deletion of MTA1 intensifies the inflammatory characteristics and adversely impacts the results of LPS-induced endometritis by altering PGE2 production.
Fig. 5: COX2 is the primary rate-limiting enzyme that contributes to the dysregulation of PGE2 production in endometritis exacerbated by MTA1 deficiency.
Fig. 6: MTA1 directly targets the Cox2 promoter (the gene encoding COX2) and inhibits its transcription in LPS-treated ESCs.
Fig. 7: Summary diagram of the possible mechanisms related to endometritis-induced MTA1 function.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank all the patients and families for participating in this study.

Funding

This work was supported by the National Natural Science Foundation of China (81972428 to Ruifang An).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, PR China

    Mao Li & Ruifang An

  2. Department of Obstetrics and Gynecology, Reproductive Medicine Center, Tangdu Hospital, Air Force Medical University (formerly known as Fourth Military Medical University), Xi’an, PR China

    Mao Li, Huan Li & Fang Liu

  3. Department of Pathology, Tangdu Hospital, Air Force Medical University (formerly known as Fourth Military Medical University), Xi’an, PR China

    Junting Li

  4. Reproductive Medicine Center, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, Shaanxi, PR China

    Yang Yang

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  1. Mao Li
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  2. Junting Li
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  3. Huan Li
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Contributions

Mao Li: Writing original draft, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. Junting Li: Validation, Methodology, Investigation, Formal analysis, Data curation. Huan Li: Validation, Methodology, Investigation. Fang Liu: Visualization, Data curation. Yang Yang: Visualization, Data curation. Ruifang An: Writing review and editing, Supervision, Funding acquisition, Formal analysis, Conceptualization. All authors have made a significant contribution to this study and approved the final manuscript.

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Correspondence to Ruifang An.

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Li, M., Li, J., Li, H. et al. MTA1-mediated transcriptional repression of Cox2 confers resistance against neutrophil infiltration in endometritis. Genes Immun (2026). https://doi.org/10.1038/s41435-026-00391-5

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