Molecular and Biochemical Mechanisms of Endometriosis

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 6829

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Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, 98122 Messina, Italy
Interests: biochemistry; molecular mechanism; oxidative stress; endometriosis
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Dear Colleagues,

Endometriosis, a gynecological condition commonly observed in women of reproductive age, is histologically characterized by the presence and growth of endometrial-like glands and stroma outside the uterine cavity and musculature which undergo cyclic proliferation and breakdown similar to that which occurs in the endometrium. This internal bleeding, which cannot leave the body and remains on site, often results in local inflammatory reactions, causing scar tissue formation and adhesions during repair processes. The local microenvironment plays a pivotal role in the onset and progression of an endometriotic lesion, as misplaced endometrial cells need to respond to local stimuli. A very recent proteomic study of peritoneal endometriotic stromal cells revealed extensive metabolic reprogramming and acquisition of cancer-like changes reflected in increased cellular invasiveness and adhesiveness, reduced apoptotic potential, and altered immune function. In this Special Issue entitled, “Molecular and Biochemical Mechanisms of Endometriosis”, we are seeking novel research or review articles highlighting the molecular mechanisms of endometriosis.

Dr. Roberta Fusco
Guest Editor

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Keywords

  • biochemistry
  • molecular pathways
  • endometriosis
  • in vivo
  • in vitro

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Published Papers (4 papers)

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Research

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11 pages, 2231 KiB  
Article
ITCH-Mediated Ubiquitylation of ITGB3 Promotes Cell Proliferation and Invasion of Ectopic Endometrial Stromal Cells in Ovarian Endometriosis
by Liansuo Zhang, Wei Shao, Mingqing Li and Songping Liu
Biomedicines 2023, 11(9), 2506; https://doi.org/10.3390/biomedicines11092506 - 11 Sep 2023
Cited by 2 | Viewed by 1285
Abstract
Post-translational modification of proteins is involved in the occurrence of endometriosis (EM); however, the role of ubiquitination modification in EM remains unclear. Integrin β3 (ITGB3) is one of the β-subunits of integrins, which plays a key role in tumor progression. In this study, [...] Read more.
Post-translational modification of proteins is involved in the occurrence of endometriosis (EM); however, the role of ubiquitination modification in EM remains unclear. Integrin β3 (ITGB3) is one of the β-subunits of integrins, which plays a key role in tumor progression. In this study, we investigated the roles of ITGB3 and ITCH, one of the ubiquitin E3 ligases, in ectopic endometrial stromal cells (ESCs) and EM. Primary ectopic ESCs and normal ESCs were isolated and purified. Western blot was used to detect the expression of ITGB3 and ITCH in ESCs. The interaction between ITGB3 and ITCH in ESCs was investigated by the co-immunoprecipitation and ubiquitylation analysis. With or without the overexpression of ITCH and/or ITGB3, the proliferation and invasion of ectopic ESCs were detected by the CCK8 assay and transwell migration assay, respectively. We found that ITGB3 is upregulated in ectopic ESCs from patients with EM. ITCH interacts with ITGB3 by co-immunoprecipitation, and ITCH-overexpressing significantly increased the ubiquitination of ITGB3. The data of the CCK8 assays showed that ITGB3 overexpression significantly promoted cell proliferation of ectopic ESCs at 12, 24, 48, and 72 h. The transwell migration assays showed that ITGB3 overexpression significantly enhanced the invasive ability. However, ITCH had the opposite effects in both assays. Our findings indicate that ITCH-mediated ubiquitylation of ITGB3 regulates the proliferation and invasion ability of ectopic ESCs in EM. Full article
(This article belongs to the Special Issue Molecular and Biochemical Mechanisms of Endometriosis)
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13 pages, 978 KiB  
Article
A Novel Classification of Endometriosis Based on Clusters of Comorbidities
by Antonio Sarria-Santamera, Yerden Yemenkhan, Milan Terzic, Miguel A. Ortega and Angel Asunsolo del Barco
Biomedicines 2023, 11(9), 2448; https://doi.org/10.3390/biomedicines11092448 - 2 Sep 2023
Cited by 3 | Viewed by 2225
Abstract
Endometriosis is a heterogeneous, complex, and still challenging disease, due to its epidemiological, etiological and pathogenic, diagnostic, therapeutic, and prognosis characteristics. The classification of endometriosis is contentious, and existing therapies show significant variability in their effectiveness. This study aims to capture and describe [...] Read more.
Endometriosis is a heterogeneous, complex, and still challenging disease, due to its epidemiological, etiological and pathogenic, diagnostic, therapeutic, and prognosis characteristics. The classification of endometriosis is contentious, and existing therapies show significant variability in their effectiveness. This study aims to capture and describe clusters of women with endometriosis based on their comorbidity. With data extracted from electronic records of primary care, this study performs a hierarchical clustering with the Ward method of women with endometriosis with a subsequent analysis of the distribution of comorbidities. Data were available for 4055 women with endometriosis, and six clusters of women were identified: cluster 1 (less comorbidity), cluster 2 (anxiety and musculoskeletal disorders), cluster 3 (type 1 allergy or immediate hypersensitivity); cluster 4 (multiple morbidities); cluster 5 (anemia and infertility); and cluster 6 (headache and migraine). Clustering aggregates similar units into similar clusters, partitioning dissimilar objects into other clusters at a progressively finer granularity—in this case, groups of women with similarities in their comorbidities. Clusters may provide a deeper insight into the multidimensionality of endometriosis and may represent diverse “endometriosis trajectories” which may be associated with specific molecular and biochemical mechanisms. Comorbidity-based clusters may be important to the scientific study of endometriosis, contributing to the clarification of its clinical complexity and variability. An awareness of those comorbidities may help elucidate the etiopathogenesis and facilitate the accurate earlier diagnosis and initiation of treatments targeted toward particular subgroups. Full article
(This article belongs to the Special Issue Molecular and Biochemical Mechanisms of Endometriosis)
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Review

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25 pages, 3786 KiB  
Review
Inflammatory Bowel Disease and Endometriosis: Diagnosis and Clinical Characteristics
by Mariasofia Fiorillo, Benedetto Neri, Roberto Mancone, Consuelo Russo, Federica Iacobini, Sara Concetta Schiavone, Elena De Cristofaro, Stefano Migliozzi, Caterina Exacoustos and Livia Biancone
Biomedicines 2024, 12(11), 2521; https://doi.org/10.3390/biomedicines12112521 - 4 Nov 2024
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Abstract
Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the [...] Read more.
Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: “Crohn’s Disease”, “Ulcerative Colitis”, “Endometriosis”, “Adenomyosis”, and “Inflammatory Bowel Disease”, individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions. Full article
(This article belongs to the Special Issue Molecular and Biochemical Mechanisms of Endometriosis)
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Other

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15 pages, 525 KiB  
Systematic Review
Atypical Endometriosis: A Comprehensive Systematic Review of Pathological Patterns and Diagnostic Challenges
by Vito Andrea Capozzi, Elisa Scarpelli, Sara dell’Omo, Martino Rolla, Alessandra Pezzani, Giovanni Morganelli, Michela Gaiano, Tullio Ghi and Roberto Berretta
Biomedicines 2024, 12(6), 1209; https://doi.org/10.3390/biomedicines12061209 - 29 May 2024
Cited by 1 | Viewed by 1808
Abstract
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as [...] Read more.
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance. Full article
(This article belongs to the Special Issue Molecular and Biochemical Mechanisms of Endometriosis)
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