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Molecular and Cellular Aspects of Endometriosis

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A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 26624

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Special Issue Editor

Prof. Dr. Martin Götte

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Guest Editor

Department of Gynecology and Obstetrics, Universitätsklinikum Münster, Munster, Germany
Interests: gynecology and obstetrics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Endometriosis is a common condition that affects approximately 6–10% of women of reproductive age. It is a chronic inflammatory disease that is associated with pelvic pain, painful periods, pain with sexual intercourse, and subfertility. The current treatment strategies for endometriosis are restricted to the surgical excision of the lesions or the suppression of ovarian function to mimic premature menopause. In up to 75% of cases, symptoms recur after surgery, and long-term ovarian suppression is often ineffective, suppresses fertility, and has unwelcome side effects. The identification of relevant molecular mechanisms that are functionally linked to the patient’s symptoms is, therefore, a major priority. This Special Issue is devoted to presenting the latest developments in uncovering the molecular and cellular mechanisms of endometriosis. These mechanisms include novel mechanisms of endocrine dysregulation, genetic and epigenetic factors and omics approaches, noncoding RNAs, aberrant stem cell function, metabolic dysregulation, changes in the inflammatory and angiogenic microenvironment, novel factors governing invasive growth, and the use of new experimental model systems including organoids and 3D coculture systems. A better understanding of the molecular mechanisms governing endometriosis is an important prerequisite for the development of new therapeutic approaches.

Prof. Dr. Martin Götte
Guest Editor

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Keywords

endometriosis
endometrium
stem cells
microRNAs
3D culture
epigenetics
inflammation
endocrine
microenvironment
organoids

Published Papers (6 papers)

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Research

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12 pages, 1191 KiB

Open AccessArticle

Epithelial Cells of Deep Infiltrating Endometriosis Harbor Mutations in Cancer Driver Genes

by Agnieszka Koppolu, Radosław B. Maksym, Wiktor Paskal, Marcin Machnicki, Beata Rak, Monika Pępek, Filip Garbicz, Kacper Pełka, Zofia Kuśmierczyk, Joanna Jacko, Małgorzata Rydzanicz, Magdalena Banach-Orłowska, Tomasz Stokłosa, Rafał Płoski, Jacek Malejczyk and Paweł K. Włodarski

Cells 2021, 10(4), 749; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10040749 - 29 Mar 2021

Cited by 7 | Viewed by 2643

Abstract

Endometriosis is an inflammatory condition manifested by the presence of endometrial-like tissue outside of the uterine cavity. The most common clinical presentations of endometriosis are dysmenorrhea, infertility, and severe pelvic pain. Few hypotheses attempt to explain the pathogenesis of endometriosis; however, none of the theories have been fully confirmed or considered universal. We examined somatic mutations in eutopic endometrium samples, deep endometriotic nodules and peripheral blood from 13 women with deep endometriosis of the rectovaginal space. Somatic variants were identified in laser microdissected samples using next-generation sequencing. A custom panel of 1296 cancer-related genes was employed, and selected genes representing cancer drivers and non-drivers for endometrial and ovarian cancer were thoroughly investigated. All 59 detected somatic variants were of low mutated allele frequency (<10%). In deep ectopic lesions, detected variants were significantly more often located in cancer driver genes, whereas in eutopic endometrium, there was no such distribution. Our results converge with other reports, where cancer-related mutations were found in endometriosis without cancer, particularly recurrent KRAS mutations. Genetic alterations located in ectopic endometriotic nodules could contribute to their formation; nevertheless, to better understand the pathogenesis of this disease, more research in this area must be performed. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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11 pages, 976 KiB

Open AccessArticle

Endometriosis Is Associated with Functional Polymorphism in the Promoter of Heme Oxygenase 1 (HMOX1) Gene

by Łukasz Milewski, Aneta Ścieżyńska, Joanna Ponińska, Marta Soszyńska, Ewa Barcz, Piotr I. Roszkowski, Paweł Kamiński, Paweł Włodarski, Rafał Płoski and Jacek Malejczyk

Cells 2021, 10(3), 695; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10030695 - 21 Mar 2021

Cited by 8 | Viewed by 2323

Abstract

Endometriosis is a common gynecological disorder characterized by the ectopic growth of endometrial-like tissue outside the uterine cavity. Etiopathogenesis of endometriosis is poorly understood; it is plausible, however, that the disease may be associated with oxidative stress related to local heme and iron metabolism. Therefore, the aim of the study was to reveal a possible association of endometriosis with a stress-inducible heme oxygenase 1 (HMOX1). For this purpose, 228 patients with clinically confirmed endometriosis and 415 control parous women from general Polish population were examined for functional –413A>T (rs2071746) single-nucleotide polymorphism (SNP) and (GT)_n dinucleotide repeat length polymorphism in the promoter of HMOX1 gene. In addition, –413A>T SNP was assessed by the specific TaqMan^® SNP Genotyping Assay, and (GT)_n polymorphism was determined by PCR product size analysis. We found that endometriosis is associated with an increased frequency of −413A(GT)_31,32 haplotype (OR (95%CI) = 1.27 (1.01–1.60), p = 0.0381) and −413A(GT)_31,32 homozygous genotype [OR (95%CI) = 1.51 (1.06–2.17), p = 0.0238]. These data suggest that endometriosis is associated with functional polymorphism of HMOX1 gene, and this gene may play a part in the pathogenesis of this disorder. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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13 pages, 2175 KiB

Open AccessArticle

CLTA-4 Expression Is Associated with the Maintenance of Chronic Inflammation in Endometriosis and Infertility

by Monika Abramiuk, Dominika Bębnowska, Rafał Hrynkiewicz, Paulina Niedźwiedzka-Rystwej, Grzegorz Polak, Jan Kotarski, Jacek Roliński and Ewelina Grywalska

Cells 2021, 10(3), 487; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10030487 - 25 Feb 2021

Cited by 9 | Viewed by 2815

Abstract

Altered immune mechanisms are implicated in the pathogenesis of endometriosis. CTLA-4 is a membrane receptor that favors the anergic state of lymphocytes, which may disrupt the immune system response in the endometriotic environment. In this study, we examined the expression of CTLA-4 on T and B cells by flow cytometry and its levels in blood serum and peritoneal fluid by ELISA. Levels of CTLA-4+ T cells were significantly higher in patients with more advanced endometriosis than in those with less advanced disease. Additionally, the negative correlation of CTLA-4⁺ T lymphocytes and the percentage of NK and NKT-like cells in women with endometriosis and infertility may indicate a different etiopathogenesis of endometriosis accompanying infertility. Our findings shed light on the potential of CTLA-4 in developing new diagnostic and therapeutic approaches in endometriosis management. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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Review

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14 pages, 929 KiB

Open AccessFeature PaperReview

Pathogenesis of Endometriosis: The Origin of Pain and Subfertility

by Teresa Mira Gruber and Sylvia Mechsner

Cells 2021, 10(6), 1381; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10061381 - 03 Jun 2021

Cited by 74 | Viewed by 10248

Abstract

Endometriosis (EM) and adenomyosis (AM) are common conditions with pain and infertility as the principal symptoms. The pathophysiology of pain in EM and AM comprises sensory and somatoform pain mechanisms. Over time, these may aggravate and lead to individual complex disease patterns if not diagnosed and treated. Despite the known facts, several years often pass between the onset of symptoms and diagnosis. Chronic pain disorders with changes on a neuronal level frequently arise and are linked to depressive disorders, with the process becoming a vicious cycle. Additionally, women with EM and AM suffer from sub- and infertility. Low fecundity rates are caused by anatomical changes in combination with behavioral changes in the sexual activity of women with chronic pain as well as local proinflammatory factors that not only decrease implantation rates but also promote early abortions. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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14 pages, 338 KiB

Open AccessReview

The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art

by Dorota Suszczyk, Wiktoria Skiba, Joanna Jakubowicz-Gil, Jan Kotarski and Iwona Wertel

Cells 2021, 10(3), 677; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10030677 - 18 Mar 2021

Cited by 9 | Viewed by 3196

Abstract

Endometriosis (EMS) is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus. Approximately 10% of women around the world suffer from this disease. Recent studies suggest that endometriosis has potential to transform into endometriosis-associated ovarian cancer (EAOC). Endometriosis is connected with chronic inflammation and changes in the phenotype, activity, and function of immune cells. The underlying mechanisms include quantitative and functional disturbances of neutrophils, monocytes/macrophages (MO/MA), natural killer cells (NK), and T cells. A few reports have shown that immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) may promote the progression of endometriosis. MDSCs are a heterogeneous population of immature myeloid cells (dendritic cells, granulocytes, and MO/MA precursors), which play an important role in the development of immunological diseases such as chronic inflammation and cancer. The presence of MDSCs in pathological conditions correlates with immunosuppression, angiogenesis, or release of growth factors and cytokines, which promote progression of these diseases. In this paper, we review the impact of MDSCs on different populations of immune cells, focusing on their immunosuppressive role in the immune system, which may be related with the pathogenesis and/or progression of endometriosis and its transformation into ovarian cancer. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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13 pages, 437 KiB

Open AccessReview

The Importance of Stromal Endometriosis in Thoracic Endometriosis

by Ezekiel Mecha, Roselydiah Makunja, Jane B. Maoga, Agnes N. Mwaura, Muhammad A. Riaz, Charles O. A. Omwandho, Ivo Meinhold-Heerlein and Lutz Konrad

Cells 2021, 10(1), 180; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10010180 - 18 Jan 2021

Cited by 7 | Viewed by 4237

Abstract

Thoracic endometriosis (TE) is a rare type of endometriosis, where endometrial tissue is found in or around the lungs and is frequent among extra-pelvic endometriosis patients. Catamenial pneumothorax (CP) is the most common form of TE and is characterized by recurrent lung collapses around menstruation. In addition to histology, immunohistochemical evaluation of endometrial implants is used more frequently. In this review, we compared immunohistochemical (CPE) with histological (CPH) characterizations of TE/CP and reevaluated arguments in favor of the implantation theory of Sampson. A summary since the first immunohistochemical description in 1998 until 2019 is provided. The emphasis was on classification of endometrial implants into glands, stroma, and both together. The most remarkable finding is the very high percentage of stromal endometriosis of 52.7% (CPE) compared to 10.2% (CPH). Chest pain, dyspnea, right-sided preference, and diaphragmatic endometrial implants showed the highest percentages in both groups. No significant association was found between the recurrence rate and the various appearances of endometriosis. Sometimes in CPE (6.8%) and CPH (30.6%) no endometrial implants were identified underlining the importance of sensitive detection of endometriosis during and after surgery. We suggest that immunohistochemical evaluation should become mandatory and will improve diagnosis and classification of the disease. Full article

(This article belongs to the Special Issue Molecular and Cellular Aspects of Endometriosis)

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