Molecular Alterations in Vaginal Wall Tissues Associated with Post-Hysterectomy Pelvic Organ Prolapse

Abstract

Objective

Hysterectomy significantly increases the risk of pelvic organ prolapse (POP). However, the underlying molecular changes remain unclear. The aim of this study was to elucidate potential molecular associations by comparing single-cell transcriptomic profiles of vaginal tissues from postmenopausal women across three groups: normal controls, POP patients with an intact uterus, and post-hysterectomy POP patients.

Methods

A single-cell transcriptomic dataset of prolapsed vaginal tissues was used to analyze genes that were differentially expressed between fibroblasts and macrophages in the two prolapse types. Key transcriptional regulators of myofibroblast differentiation were identified. Cell subtypes were identified, and macrophage polarization states were assessed to evaluate immune responses in different POP subtypes.

Results

Post-hysterectomy POP patients exhibited impaired myofibroblast differentiation, downregulated expression of wound-healing genes, and disrupted extracellular matrix (ECM) remodeling. In contrast, uterus-intact POP patients showed stronger immune activation, enhanced fibroblast‒macrophage crosstalk, and upregulated expression of genes related to leukocyte-mediated immunity. Key transcriptional regulators were linked to myofibroblast differentiation. Macrophage profiling revealed predominant M2 polarization in post-hysterectomy patients, indicating a potential compensatory response to biomechanical instability, whereas uterus-intact POP patients maintained more active immune responses.

Conclusion

This study revealed that hysterectomy alters vaginal homeostasis through ECM disorganization, impaired wound healing, and macrophage reprogramming. Our findings highlight distinct molecular changes in fibroblasts and macrophages between uterus-intact POP patients and post-hysterectomy POP patients, advancing the understanding of POP pathogenesis.

Keywords

Pelvic organ prolapse / Hysterectomy / Single-cell transcriptomics / Macrophage polarization / Extracellular matrix remodeling / Myofibroblast differentiation

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Funding

National High Level Hospital Clinical Research Funding(2026-PUMCH-A-050)

Peking Union Medical College Hospital Talent Cultivation Program (Category C)(UBJ12052)

the Independent Research Fund of the State Key Laboratory of Catalysis, Severe, and Rare Diseases(2025-I-PY-010)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology

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