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Endometriosis: Focusing on Molecular and Cellular Research, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 August 2026 | Viewed by 1199

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Guest Editor
Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy
Interests: electrochemotherapy; cancer; cell culture; gene expression; immunohistochemistry; cell signaling; apoptosis; cell proliferation; cancer biomarkers; regression analysis; phosphorylation; diagnosis; endometriosis; melanoma; osteoarthritis; articular cartilage; p53; chondrocytes; mesothelioma
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Special Issue Information

Dear Colleagues,

Endometriosis is a common disease in the reproductive system that affects approximately 6–10% of women of reproductive age. This disease involves the presence of endometrial cells, glands, and stroma outside the uterus, resulting in symptoms such as pelvic pain, painful periods, pain during sexual intercourse, and subfertility. Despite the great advances made in diagnostics, pharmacology, minimally invasive surgery, and assisted reproduction technologies, endometriosis still represents an unsolved global health issue. The theory still most accepted today regarding its pathogenesis is that of retrograde menstruation, proposed by Sampson about a century ago. Other theories propose phenomena such as the metaplasia of coelomic tissue or activation of stem cells. Recently, an alteration of the organogenesis processes of the uterus has been proposed as a pathogenetic mechanism of endometriosis.

Endometriosis is an estrogen-dependent condition characterized by elevated estrogen receptor β (ERβ) expression, which suppresses ERα, resulting in a high ERβ/ERα ratio. ERβ contributes to disease progression by modulating apoptosis, mitochondrial function (via NRF1), and oxidative stress (through SOD2 regulation). It also upregulates inflammatory mediators such as COX2 and MMP1, promoting tissue invasion and lesion growth. Recent studies suggest that alterations in the molecular mechanisms regulating adenogenesis and the survival of endometrial structures are closely linked to the development and persistence of endometriotic lesions outside the uterus. Moreover, the chronic inflammatory environment and oxidative stress present in endometriotic lesions may promote genetic and epigenetic alteration, which is possibly responsible for the survival and growth of the endometriosis structures outside of the uterus.

This Special Issue aims to publish advanced research and review articles to allow readers to gain a better understanding of the molecular mechanisms governing endometriosis and the important prerequisites for the development of new therapeutic approaches.

Prof. Dr. Alfonso Baldi
Guest Editor

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Keywords

  • endometriosis
  • reproductive system
  • endometrial cell
  • novel treatment

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Published Papers (1 paper)

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Review

30 pages, 3629 KB  
Review
The AGE–RAGE Pathway in Endometriosis: A Focused Mechanistic Review and Structured Evidence Map
by Canio Martinelli, Alfredo Ercoli, Francesco De Seta, Marcella Barbarino, Antonio Giordano and Salvatore Cortellino
Int. J. Mol. Sci. 2026, 27(3), 1396; https://doi.org/10.3390/ijms27031396 - 30 Jan 2026
Viewed by 943
Abstract
High Mobility Group Box 1 (HMGB1) and S100 proteins are major ligands of Receptor for Advanced Glycation End-products (RAGE) and have causal roles in endometriosis lesions. Yet the AGE–RAGE pathway that unifies Advanced Glycation End-products (AGEs) with these ligands has not been assessed [...] Read more.
High Mobility Group Box 1 (HMGB1) and S100 proteins are major ligands of Receptor for Advanced Glycation End-products (RAGE) and have causal roles in endometriosis lesions. Yet the AGE–RAGE pathway that unifies Advanced Glycation End-products (AGEs) with these ligands has not been assessed in endometriosis. In diabetes, atherosclerosis, and chronic kidney disease, AGE–RAGE links insulin resistance and oxidative stress to inflammation, fibrosis, and organ harm. Endometriosis shares key drivers of AGE accumulation, including insulin resistance, oxidative stress, and chronic inflammation. Endometriosis is also linked to higher vascular risk and arterial stiffness. We asked whether AGE–RAGE could bridge metabolic stress to pelvic lesions and systemic risk. We did a focused review of mechanisms and an evidence map of studies on AGEs, RAGE, or known RAGE ligands in endometriosis. We grouped findings as most consistent with a driver, amplifier, consequence, or parallel role. We included 29 studies across human samples, cell systems, and animal models. Few studies measured AGE adducts directly. Most work tracked RAGE ligands (mainly HMGB1 and S100 proteins) and downstream immune and angiogenic programs. Across models, this pattern fits best with a self-reinforcing loop after lesions form. RAGE expression often aligned with lesion remodeling, especially fibrosis. Blood and skin readouts of AGE burden were mixed and varied by cohort and sample type. A central gap is receptor proof. Many models point to shared Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signaling, but few test RAGE dependence. Overall, current evidence supports AGE–RAGE as a disease-amplifying loop involved in chronic inflammation and fibrosis rather than an initiating trigger. Its effects likely vary by stage and site. Priorities now include direct lesion AGE measurement, paired systemic–pelvic sampling over time, receptor-level studies, and trials testing diet or drug interventions against clear endpoints. Outcomes could include fibrosis, angiogenesis, immune state, pain, and oocyte and follicle function. Full article
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