Is Recurrent Endometriosis a Reprogrammed Disease? Molecular Persistence Beyond Surgical Clearance.
Mario Palumbo1, Luigi Della Corte2, Maria Rotonda Conte1
1Department of Public Health, School of Medicine, University of Naples "Federico II", 80131 Naples, Italy.
Cells
|May 27, 2026
Summary
Endometriosis may be a molecularly reprogrammed disease, not just localized lesions. Persistent cellular and microenvironmental changes drive recurrence, suggesting surgery alone is insufficient for endometriosis treatment.
Area of Science:
- Gynecology
- Molecular Biology
- Immunology
Background:
- Endometriosis is traditionally viewed as localized ectopic endometrial tissue.
- High recurrence rates challenge the lesion-based paradigm, suggesting deeper biological mechanisms.
- Endometriotic cells show persistent molecular alterations, including gene dysregulation and immune dysfunction.
Purpose of the Study:
- To investigate if endometriosis is a molecularly reprogrammed disease.
- To determine if cellular and microenvironmental alterations persist post-surgery.
- To understand mechanisms driving endometriosis persistence and recurrence.
Main Methods:
- Narrative literature review (PubMed, Scopus, Web of Science, Jan 2016-Mar 2026).
- Included studies on molecular, genetic, epigenetic, and immunological factors.
- Focused on pathways in cellular survival, inflammation, hormone resistance, and epigenetics.
Main Results:
- Endometriotic cells exhibit stable gene expression changes (estrogen, progesterone resistance, inflammation, proliferation).
- Epigenetic modifications (DNA methylation, histone changes) create 'molecular memory'.
- Peritoneal microenvironment shows chronic inflammation, immune tolerance, and impaired cell clearance, supporting persistence.
Conclusions:
- Endometriosis is a persistent, molecularly reprogrammed disease.
- Stable cellular and microenvironmental alterations drive disease persistence.
- Surgical treatment may be insufficient; future therapies need to target molecular and immunological mechanisms.
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