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Advances in the Diagnostics of Endometriosis
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Advances in the Diagnostics of Endometriosis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 26226

Special Issue Editor

Prof. Dr. Jeong Sook Kim

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Guest Editor
Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Ulsan University Hospital, 877 Bangeojinsunwhando-ro, Dong-gu, Ulsan 44033, Korea
Interests: Reproductive endocrinology

Special Issue Information

Dear Colleagues,

Endometriosis is a commonly occurring gynaecological disorder that may cause pelvic pain and subfertility or infertility. The diagnosis of endometriosis is pathologically confirmed by the ectopic presence of endometrial-like epithelium and stroma. Although several pathogenic theories have been suggested, the exact underlying mechanisms of endometriosis still remain unclear. The long-term management of endometriosis-related symptoms and recurrence after surgery also remains a challenge. Understanding the endometrial cellular expression of certain genes and proteins may result in the improved diagnosis and treatment of endometriosis.

To expand our clinical knowledge on endometriosis, a new insight into the molecular and genetic approach for diagnosis and evaluation is required. So, we would like to discuss current advances in the molecular mechanisms of endometriosis in this Special Issue. 

Prof. Dr. Jeong Sook Kim
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. Diagnostics 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 2600 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

  • endometriosis
  • female infertility
  • chronic pelvic pain
  • molecular diagnosis of endometriosis

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Published Papers (7 papers)

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13 pages, 1136 KiB  
Article
Cell-Free DNA as a New Biomarker of IVF Success, Independent of Any Infertility Factor, Including Endometriosis
by Maria Manuel Casteleiro Alves, Luísa Oliani, Micaela Almeida, Henrique José Cardoso, António Hélio Oliani, Luiza Breitenfeld and Ana Cristina Ramalhinho
Diagnostics 2023, 13(2), 208; https://doi.org/10.3390/diagnostics13020208 - 5 Jan 2023
Cited by 3 | Viewed by 2967
Abstract
Cell-free DNA fragments detected in blood and in other biological fluids are released from apoptotic/necrotic cells. In this study, we analyzed cfDNA levels in follicular fluid (FF) samples from patients with infertility. Samples were collected from 178 infertile women and cfDNA was extracted [...] Read more.
Cell-free DNA fragments detected in blood and in other biological fluids are released from apoptotic/necrotic cells. In this study, we analyzed cfDNA levels in follicular fluid (FF) samples from patients with infertility. Samples were collected from 178 infertile women and cfDNA was extracted and quantified by qPCR, using ALU115 and ALU247 primers, and statistical correlations were performed. We found that cfDNA concentration was significantly higher in FF pools from women aged 35 and over than in women under 35 years of age (p = 0.017). We also found that q247 cfDNA levels were significantly higher in women with an associated female factor, such as endometriosis, PCOS and POF, compared with women with no specific cause of infertility (p = 0.033). The concentration of cfDNA did not vary significantly in each group of women with an associated female factor. The concentration of cfDNA was significantly higher in the FF of women that obtained embryos with a high fragmentation rate, compared to embryos with a low fragmentation rate (p = 0.007). Finally, we found that women who did not become pregnant during IVF treatments had higher q247 cfDNA levels (p = 0.043). The quantification of cfDNA could be an important biomarker of follicular micro-environment quality to predict embryo quality and the success of IVF, making them more specific and effective. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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11 pages, 844 KiB  
Article
Endometriosis Associated-miRNome Analysis of Blood Samples: A Prospective Study
by Sofiane Bendifallah, Yohann Dabi, Stéphane Suisse, Léa Delbos, Mathieu Poilblanc, Philippe Descamps, Francois Golfier, Ludmila Jornea, Delphine Bouteiller, Cyril Touboul, Anne Puchar and Emile Daraï
Diagnostics 2022, 12(5), 1150; https://doi.org/10.3390/diagnostics12051150 - 5 May 2022
Cited by 7 | Viewed by 4318
Abstract
The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain [...] Read more.
The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis. miRNA sequencing was performed using an Novaseq6000 sequencer (Illumina, San Diego, CA, USA). Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads. A total of 2633 miRNAs were found differentially expressed. Among them, 8.6% (n = 229) were up- or downregulated. For these 229 miRNAs, the F1-score, sensitivity, specificity, and AUC ranged from 0–88.2%, 0–99.4%, 4.3–100%, and 41.5–68%, respectively. Utilizing the combined bioinformatic and NGS approach, a specific and broad panel of miRNAs was detected as being potentially suitable for building a blood signature of endometriosis. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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15 pages, 683 KiB  
Article
Endometrium as Control of Endometriosis in Experimental Research: Assessment of Sample Suitability
by Vince Szegeczki, László Fazekas, Máté Kulcsár, Dora Reglodi, Péter Török, Brigitta Orlik, Antonio Simone Laganà, Attila Jakab and Tamas Juhasz
Diagnostics 2022, 12(4), 970; https://doi.org/10.3390/diagnostics12040970 - 12 Apr 2022
Cited by 6 | Viewed by 3142
Abstract
Endometriosis is a chronic gynecological disease that causes numerous severe symptoms in affected women. Revealing alterations of the molecular processes in ectopic endometrial tissue is the current policy for understanding the pathomechanisms and discovering potential novel therapeutic targets. Examining molecular processes of eutopic [...] Read more.
Endometriosis is a chronic gynecological disease that causes numerous severe symptoms in affected women. Revealing alterations of the molecular processes in ectopic endometrial tissue is the current policy for understanding the pathomechanisms and discovering potential novel therapeutic targets. Examining molecular processes of eutopic endometrium is likely to be a convenient method to compare it with the molecular alterations observed in ectopic tissues. The aim of the present study was to determine what proportion of the surgically resected eutopic endometrial samples is suitable for further experiments so that these can be comparable with endometriosis. Final hospital reports and histopathology reports of a 3-year-long period (1162 cases) were analysed. The application of a retrospective screening method promoted the categorization of these cases, and quantification of the categorized cases was accomplished. In addition, results obtained from cultured endometrium samples were also detailed. Only a small number of the harvested endometrial samples was suitable for further molecular analysis, while preoperative screening protocol could enlarge this fraction. Applying clinical and histopathological selection and exclusion criteria for tissue screening and histopathological examination of samples could ensure the comparability of healthy endometrium with endometriosis. The present study could be useful for researchers who intend to perform molecular experiments to compare endometriosis with the physiological processes of the endometrium. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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15 pages, 4188 KiB  
Article
Impaired Expression of Membrane Type-2 and Type-3 Matrix Metalloproteinases in Endometriosis but Not in Adenomyosis
by Jane B. Maoga, Muhammad A. Riaz, Agnes N. Mwaura, Georgios Scheiner-Bobis, Ezekiel Mecha, Charles O. A. Omwandho, Ivo Meinhold-Heerlein and Lutz Konrad
Diagnostics 2022, 12(4), 779; https://doi.org/10.3390/diagnostics12040779 - 22 Mar 2022
Cited by 2 | Viewed by 2379
Abstract
Matrix metalloproteinases (MMPs) play an important role in menstruation and endometriosis; however, the membrane-type matrix metalloproteinases (MT-MMPs) are not well studied in endometriosis and adenomyosis. We analyzed MT2-MMP (MMP15) and MT3-MMP (MMP16) in eutopic endometrium with and without endometriosis and with and without [...] Read more.
Matrix metalloproteinases (MMPs) play an important role in menstruation and endometriosis; however, the membrane-type matrix metalloproteinases (MT-MMPs) are not well studied in endometriosis and adenomyosis. We analyzed MT2-MMP (MMP15) and MT3-MMP (MMP16) in eutopic endometrium with and without endometriosis and with and without adenomyosis and ectopic endometrium of deep infiltrating endometriosis (DIE), peritoneal endometriosis (PE), and ovarian endometriosis (Ov) by immunohistochemistry. Preferential expression of both proteins was observed in the glandular and luminal epithelial cells of the eutopic endometrium of patients with and without endometriosis with a ~2.5-fold stronger expression of MT3-MMP compared to MT2-MMP. We did not observe any differences during menstrual cycling and in eutopic endometrium of patients with and without endometriosis. Similarly, eutopic endometrium and adenomyotic tissue with and without endometriosis showed similar protein levels of MT2-MMP and MT3-MMP. In contrast, MT2-MMP and MT3-MMP protein was decreased in ectopic compared to eutopic endometrium and adenomyosis. The similar expression of MT2-MMP and MT3-MMP in eutopic endometrium in patients with and without endometriosis in contrast to the impaired expression in ectopic endometrium suggests that alterations occur after and not before endometrial implantation possibly by distinct interactions with the different environments. The differential protein expression of MT2/3-MMP in adenomyosis compared to endometriosis might suggest a different pathogenesis pathway for the two diseases. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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20 pages, 3679 KiB  
Article
The Eutopic Endometrium Proteome in Endometriosis Reveals Candidate Markers and Molecular Mechanisms of Physiopathology
by Loren Méar, Emmanuelle Com, Khadija Fathallah, Laetitia Guillot, Régis Lavigne, Blandine Guével, Arnaud Fauconnier, François Vialard and Charles Pineau
Diagnostics 2022, 12(2), 419; https://doi.org/10.3390/diagnostics12020419 - 6 Feb 2022
Cited by 15 | Viewed by 3103
Abstract
Endometriosis is a common chronic gynaecological disease causing various symptoms, such as infertility and chronic pain. The gold standard for its diagnosis is still laparoscopy and the biopsy of endometriotic lesions. Here, we aimed to compare the eutopic endometrium from women with or [...] Read more.
Endometriosis is a common chronic gynaecological disease causing various symptoms, such as infertility and chronic pain. The gold standard for its diagnosis is still laparoscopy and the biopsy of endometriotic lesions. Here, we aimed to compare the eutopic endometrium from women with or without endometriosis to identify proteins that may be considered as potential biomarker candidates. Eutopic endometrium was collected from patients with endometriosis (n = 4) and women without endometriosis (n = 5) during a laparoscopy surgery during the mid-secretory phase of their menstrual cycle. Total proteins from tissues were extracted and digested before LC-MS-MS analysis. Among the 5301 proteins identified, 543 were differentially expressed and enriched in two specific KEGG pathways: focal adhesion and PI3K/AKT signaling. Integration of our data with a large-scale proteomics dataset allowed us to highlight 11 proteins that share the same trend of dysregulation in eutopic endometrium, regardless of the phase of the menstrual cycle. Our results constitute the first step towards the identification of potential promising endometrial diagnostic biomarkers. They provide new insights into the mechanisms underlying endometriosis and its etiology. Our results await further confirmation on a larger sample cohort. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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20 pages, 17506 KiB  
Article
Clues for Improving the Pathophysiology Knowledge for Endometriosis Using Plasma Micro-RNA Expression
by Yohann Dabi, Stéphane Suisse, Ludmila Jornea, Delphine Bouteiller, Cyril Touboul, Anne Puchar, Emile Daraï and Sofiane Bendifallah
Diagnostics 2022, 12(1), 175; https://doi.org/10.3390/diagnostics12010175 - 12 Jan 2022
Cited by 12 | Viewed by 5004 | Correction
Abstract
The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective “ENDO-miRNA” study were analyzed [...] Read more.
The pathophysiology of endometriosis remains poorly understood. The aim of the present study was to investigate functions and pathways associated with the various miRNAs differentially expressed in patients with endometriosis. Plasma samples of the 200 patients from the prospective “ENDO-miRNA” study were analyzed and all known human miRNAs were sequenced. For each miRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis. miRNAs with an AUC ≥ 0.6 were selected for further analysis. A comprehensive review of recent articles from the PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases was performed to identify functions and pathways associated with the selected miRNAs. In total, 2633 miRNAs were found in the patients with endometriosis. Among the 57 miRNAs with an AUC ≥ 0.6: 20 had never been reported before; one (miR-124-3p) had previously been observed in endometriosis; and the remaining 36 had been reported in benign and malignant disorders. miR-124-3p is involved in ectopic endometrial cell proliferation and invasion and plays a role in the following pathways: mTOR, STAT3, PI3K/Akt, NF-κB, ERK, PLGF-ROS, FGF2-FGFR, MAPK, GSK3B/β–catenin. Most of the remaining 36 miRNAs are involved in carcinogenesis through cell proliferation, apoptosis, and invasion. The three main pathways involved are Wnt/β–catenin, PI3K/Akt, and NF–KB. Our results provide evidence of the relation between the miRNA profiles of patients with endometriosis and various signaling pathways implicated in its pathophysiology. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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6 pages, 1746 KiB  
Case Report
Ruptured Hemorrhagic Ectopic Pregnancy Implanted in the Diaphragm: A Rare Case Report and Brief Literature Review
by Ok Ju Kang, Ji Hye Koh, Ji Eun Yoo, So Yeon Park, Jeong-Ik Park, Songsoo Yang, Sang-Hun Lee, Soo-Jeong Lee, Jun-Woo Ahn, Hyun-Jin Roh and Jeong Sook Kim
Diagnostics 2021, 11(12), 2342; https://doi.org/10.3390/diagnostics11122342 - 13 Dec 2021
Cited by 2 | Viewed by 4304
Abstract
The mortality and morbidity rates of non-tubal ectopic pregnancies with abdominal hemorrhaging are 7–8 times higher than those of tubal pregnancies. Diaphragmatic pregnancy is a rare non-tubal ectopic form, causing acute abdominal hemoperitoneum. Here, we present a case of a primary diaphragmatic ectopic [...] Read more.
The mortality and morbidity rates of non-tubal ectopic pregnancies with abdominal hemorrhaging are 7–8 times higher than those of tubal pregnancies. Diaphragmatic pregnancy is a rare non-tubal ectopic form, causing acute abdominal hemoperitoneum. Here, we present a case of a primary diaphragmatic ectopic pregnancy with hemorrhage that was immediately diagnosed and successfully managed with laparoscopic surgery. Rapid and accurate diagnosis using appropriate imaging modalities is critical for improving the prognosis of a child-bearing woman with an abdominal pregnancy. Full article
(This article belongs to the Special Issue Advances in the Diagnostics of Endometriosis)
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