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Cells
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Molecular Advances and New Therapeutic Approaches in Endometriosis
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Molecular Advances and New Therapeutic Approaches in Endometriosis

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

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 7022

Special Issue Editor

Dr. Lutz Konrad

E-Mail Website
Guest Editor
Center of Gynecology and Obstetrics, Faculty of Medicine, Justus-Liebig-University Giessen, Feulgenstr. 10-12, D-35392 Giessen, Germany
Interests: pathogenesis; TGF-betas; in vitro models; epithelial–mesenchymal transition; non-invasive diagnostics; pain

Special Issue Information

Dear Colleagues,

The human endometrium is unique because it is a highly regenerative tissue and heals without scarring. Menstruation generates not only pain but also, via retrograde menstruation, contributes to endometriosis. Although Sampson’s implantation hypothesis is generally accepted as the most likely cause of endometriosis, more hypotheses, such as inflammation, hypoxia etc., are needed to explain why only a minor fraction of women get the disease.

The aim of this Special Issue is to highlight molecular pathways involved in endometriosis that can help to develop or improve new and existing therapies, especially with respect to pain. The main focus will be on in vitro and animal models.

Areas to be included in this Special Issue are focused on but not limited to: molecular pathways, new therapies, pathogenesis, stem cells, stromal/mesenchymal cells, epithelial cells, epithelial–mesenchymal transition, migration, invasion, pain, in vitro models, animal model organoids, 3D models and architectures, non-invasive diagnostics, next-generation single cell sequencing, and array analysis.

We hope that this Special Issue will broaden and deepen our knowledge on endometriosis with respect to the topics mentioned above, and that it will be of interest to both scientists and clinicians. Thus, contributions by experts in the field of endometriosis, in the form of original research articles and/or reviews, are most welcome. 

Dr. Lutz Konrad
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapies
  • pathogenesis
  • stem cells
  • stromal/mesenchymal cells
  • epithelial cells
  • epithelial–mesenchymal transition
  • pain
  • in vitro models
  • animal model organoids
  • 3D models
  • non-invasive diagnostics
  • next-generation single-cell sequencing
  • array analysis

Published Papers (4 papers)

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Research

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22 pages, 3876 KiB  
Article
Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis
by Sushma Marla, Sally Mortlock, Sohye Yoon, Joanna Crawford, Stacey Andersen, Michael D. Mueller, Brett McKinnon, Quan Nguyen and Grant W. Montgomery
Cells 2023, 12(13), 1736; https://doi.org/10.3390/cells12131736 - 28 Jun 2023
Viewed by 1443
Abstract
Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with [...] Read more.
Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with (n = 4) and without endometriosis (n = 4). ESC TSSs and enhancers were compared to those reported in other tissue and cell types in FANTOM5 and were integrated with RNA-seq and ATAC-seq data from the same samples for regulatory activity and network analyses. CAGE tag count differences between women with and without endometriosis were statistically tested and tags within close proximity to genetic variants associated with endometriosis risk were identified. Over 90% of tag clusters mapping to promoters were observed in cells and tissues in FANTOM5. However, some potential cell-type-specific promoters and enhancers were also observed. Regions of open chromatin identified using ATAC-seq provided further evidence of the active transcriptional regions identified by CAGE. Despite the small sample number, there was evidence of differences associated with endometriosis at 210 consensus clusters, including IGFBP5, CALD1 and OXTR. ESC TSSs were also located within loci associated with endometriosis risk from genome-wide association studies. This study provides novel evidence of transcriptional differences in endometrial stromal cells associated with endometriosis and provides a valuable cell-type specific resource of active TSSs and enhancers in endometrial stromal cells. Full article
(This article belongs to the Special Issue Molecular Advances and New Therapeutic Approaches in Endometriosis)
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10 pages, 2905 KiB  
Article
Nociceptin/Orphanin FQ Opioid Peptide-Receptor Expression in the Endometriosis-Associated Nerve Fibers—Possible Treatment Option?
by Qihui Guan, Renata Voltolini Velho, Alice Jordan, Sabrina Pommer, Irene Radde, Jalid Sehouli and Sylvia Mechsner
Cells 2023, 12(10), 1395; https://doi.org/10.3390/cells12101395 - 15 May 2023
Cited by 1 | Viewed by 1382
Abstract
Endometriosis (EM) is a chronic inflammatory disease affecting millions of women worldwide. Chronic pelvic pain is one of the main problems of this condition, leading to quality-of-life impairment. Currently, available treatment options are not able to treat these women accurately. A better understanding [...] Read more.
Endometriosis (EM) is a chronic inflammatory disease affecting millions of women worldwide. Chronic pelvic pain is one of the main problems of this condition, leading to quality-of-life impairment. Currently, available treatment options are not able to treat these women accurately. A better understanding of the pain mechanisms would be beneficial to integrate additional therapeutic management strategies, especially specific analgesic options. To understand pain in more detail, nociceptin/orphanin FQ peptide (NOP) receptor expression was analyzed in EM-associated nerve fibers (NFs) for the first time. Laparoscopically excised peritoneal samples from 94 symptomatic women (73 with EM and 21 controls) were immunohistochemically stained for NOP, protein gene product 9.5 (PGP9.5), substance P (SP), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). Peritoneal NFs of EM patients and healthy controls were positive for NOP and often colocalized with SP-, CGRP-, TH-, and VIP-positive nerve fibers, suggesting that NOP is expressed in sensory and autonomic nerve fibers. In addition, NOP expression was increased in EM associate NF. Our findings highlight the potential of NOP agonists, particularly in chronic EM-associated pain syndromes and deserve further study, as the efficacy of NOP-selective agonists in clinical trials. Full article
(This article belongs to the Special Issue Molecular Advances and New Therapeutic Approaches in Endometriosis)
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Review

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14 pages, 684 KiB  
Review
The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities
by Iason Psilopatis, Kleio Vrettou, Florian Nima Fleckenstein and Stamatios Theocharis
Cells 2023, 12(9), 1227; https://doi.org/10.3390/cells12091227 - 23 Apr 2023
Cited by 4 | Viewed by 1571
Abstract
Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone [...] Read more.
Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the particular role of HDACs and their inhibitors in the context of endometriosis. HDAC1, HDAC2, HDAC3, Sirtuin 1, and Sirtuin 3, are the five most studied HDAC enzymes which seem to, at least partly, influence the pathophysiology of endometriosis. Both well-established and novel HDACIs could possibly represent modern, efficacious anti-endometriotic drug agents. Altogether, histone modifications and their therapeutic targeting have been proven to have a strong impact on endometriosis. Full article
(This article belongs to the Special Issue Molecular Advances and New Therapeutic Approaches in Endometriosis)
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Other

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20 pages, 1088 KiB  
Systematic Review
Vascularisation in Deep Endometriosis: A Systematic Review with Narrative Outcomes
by Simon G. Powell, Priyanka Sharma, Samuel Masterson, James Wyatt, Ilyas Arshad, Shakil Ahmed, Gendie Lash, Michael Cross and Dharani K. Hapangama
Cells 2023, 12(9), 1318; https://doi.org/10.3390/cells12091318 - 05 May 2023
Cited by 2 | Viewed by 2174
Abstract
Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of [...] Read more.
Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE. Full article
(This article belongs to the Special Issue Molecular Advances and New Therapeutic Approaches in Endometriosis)
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