Advanced Research in Endometriosis 3.0

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 29669

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Guest Editor
Department Obstetrics/Gynaecology, Northwick Park Hospital, London North West University Healthcare NHS Trust, Watford Rd, Harrow HA1 3UJ, London, UK
Interests: endometriosis; pain; inflammation; inhibitors
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Special Issue Information

Dear Colleagues,

Endometriosis is a chronic, inflammatory, benign disease commonly found in women of reproductive age. However, it can affect people of all ages and has even been found in men and animals, as well as in fetuses. Unfortunately, it tends to take 7–10 years for the diagnosis of endometriosis to be made. This Special Issue provides an excellent opportunity for a thorough analysis of the pathophysiology of the disease, the signs and symptoms, and the type of pain. Categories of endometriosis can be identified, and conservative and surgical techniques can be provided. An important research area is the pain associated with endometriosis. One of the causative factors of the pain experienced in endometriosis is inflammation. The suppression of inflammatory mediators by inhibiting their synthesis might offer novel and effective treatments for the inflammatory pain experienced in endometriosis. This Special Issue welcomes new and innovative original studies and detailed reviews in this field.

Dr. Nikolaos Machairiotis
Guest Editor

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Keywords

  • mutations
  • biomarkers
  • diagnosis
  • treatment
  • pelvic pain
  • endometriosis
  • patient care
  • imaging
  • infertility
  • inhibitors
  • comorbidity
  • recurrence

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Published Papers (10 papers)

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Research

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18 pages, 1714 KiB  
Article
Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder
by Michela Cirillo, Flavia Rita Argento, Monica Attanasio, Matteo Becatti, Irene Ladisa, Claudia Fiorillo, Maria Elisabetta Coccia and Cinzia Fatini
Biomedicines 2023, 11(2), 450; https://doi.org/10.3390/biomedicines11020450 - 3 Feb 2023
Cited by 5 | Viewed by 3351
Abstract
Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective [...] Read more.
Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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10 pages, 303 KiB  
Article
Plasma and Peritoneal Fluid ZEB Levels in Patients with Endometriosis and Infertility
by Paweł Bartnik, Joanna Kacperczyk-Bartnik, Ksawery Goławski, Janusz Sierdziński, Grzegorz Mańka, Mariusz Kiecka, Michał Lipa, Damian Warzecha, Robert Spaczyński, Piotr Piekarski, Beata Banaszewska, Artur J. Jakimiuk, Tadeusz Issat, Wojciech Rokita, Jakub Młodawski, Maria Szubert, Piotr Sieroszewski, Grzegorz Raba, Kamil Szczupak, Tomasz Kluz, Marek Kluza, Krzysztof Czajkowski, Mirosław Wielgoś, Ewa Koc-Żórawska, Marcin Żórawski and Piotr Laudańskiadd Show full author list remove Hide full author list
Biomedicines 2022, 10(10), 2460; https://doi.org/10.3390/biomedicines10102460 - 1 Oct 2022
Cited by 6 | Viewed by 2106
Abstract
Zinc finger E-box-binding homeobox 1 (ZEB1) and zinc finger E-box-binding homeobox 2 (ZEB2) are transcription factors that regulate epithelial–mesenchymal transformation (EMT). The aim of this study was to compare levels of ZEB1 and ZEB2 in the peritoneal fluid and plasma between patients with [...] Read more.
Zinc finger E-box-binding homeobox 1 (ZEB1) and zinc finger E-box-binding homeobox 2 (ZEB2) are transcription factors that regulate epithelial–mesenchymal transformation (EMT). The aim of this study was to compare levels of ZEB1 and ZEB2 in the peritoneal fluid and plasma between patients with and without endometriosis in order to assess their utility in the diagnostic process. Plasma and peritoneal fluid samples were collected from 50 patients with and 48 without endometriosis during planned surgical procedures in eight clinical centers. Quantitative ZEB1 and ZEB2 levels analyses were performed using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in ZEB1 levels in any of the subanalyses nor any differences regarding ZEB2 levels between patients with and without endometriosis. Plasma ZEB2 levels were significantly higher among patients with infertility compared to fertile women (16.07 ± 12.70 ng/L vs. 12.07 ± 11.92 ng/L; p < 0.04). Both ZEB1 and ZEB2 do not seem to have a significant value in the initial diagnosis of endometriosis as a single marker. The differences in ZEB2 plasma levels between patients with and without infertility indicate the possibility of EMT dysregulation in the pathogenesis of adverse fertility outcomes. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
10 pages, 287 KiB  
Article
Plasma and Peritoneal Poly (ADP-Ribose) Polymerase Levels in Patients with Endometriosis
by Joanna Kacperczyk-Bartnik, Paweł Bartnik, Ksawery Goławski, Janusz Sierdziński, Grzegorz Mańka, Mariusz Kiecka, Michał Lipa, Damian Warzecha, Robert Spaczyński, Piotr Piekarski, Beata Banaszewska, Artur Jakimiuk, Tadeusz Issat, Wojciech Rokita, Jakub Młodawski, Maria Szubert, Piotr Sieroszewski, Grzegorz Raba, Kamil Szczupak, Tomasz Kluz, Marek Kluza, Krzysztof Czajkowski, Mirosław Wielgoś, Ewa Koc-Żórawska, Marcin Żórawski and Piotr Laudańskiadd Show full author list remove Hide full author list
Biomedicines 2022, 10(10), 2451; https://doi.org/10.3390/biomedicines10102451 - 1 Oct 2022
Cited by 4 | Viewed by 1676
Abstract
The evidence of poly (ADP-ribose) polymerase (PARP) association with the immune response could be coherent with the immunological theory of endometriosis and suggests the possibility of a new research direction. The aim of the study was to evaluate the levels of PARP in [...] Read more.
The evidence of poly (ADP-ribose) polymerase (PARP) association with the immune response could be coherent with the immunological theory of endometriosis and suggests the possibility of a new research direction. The aim of the study was to evaluate the levels of PARP in plasma and peritoneal fluid of patients with and without endometriosis. It was a multicenter, cross-sectional study. Plasma and peritoneal fluid samples were collected from patients with and without endometriosis during planned laparoscopic procedures in eight clinical centers. In total, 84 samples of plasma and 84 samples of the peritoneal fluid were included in the final analyses. Double-antibody sandwich enzyme-linked immunosorbent assay was performed in order to assess levels of PARP in collected samples. No statistically significant differences regarding the detected levels of PARP in plasma and peritoneal fluid comparing patients with and without endometriosis were observed. Patients with a history of infertility had significantly higher plasma PARP concentrations (p = 0.04). We have not observed the potential role of PARP concentration levels in plasma nor peritoneal fluid as an endometriosis biomarker. We have determined an association between a higher plasma PARP concentration and a history of infertility. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
11 pages, 2053 KiB  
Article
Transcriptome Profiling of Eutopic and Ectopic Endometrial Stromal Cells in Women with Endometriosis Based on High-Throughput Sequencing
by Chih-Chieh Chen, Yung-Che Chou, Chia-Yi Hsu, Eing-Mei Tsai and Tze-Kiong Er
Biomedicines 2022, 10(10), 2432; https://doi.org/10.3390/biomedicines10102432 - 29 Sep 2022
Cited by 3 | Viewed by 1777
Abstract
Endometriosis is a common gynecological disease that affects approximately 5–10% of reproductive-aged women. However, the etiology and pathophysiology of endometriosis are currently unclear. The objective of this study was to identify a potential pathogenic gene of endometriosis using RNA sequencing (RNA-seq) analysis. Human [...] Read more.
Endometriosis is a common gynecological disease that affects approximately 5–10% of reproductive-aged women. However, the etiology and pathophysiology of endometriosis are currently unclear. The objective of this study was to identify a potential pathogenic gene of endometriosis using RNA sequencing (RNA-seq) analysis. Human endometrial stromal cells were isolated from four patients receiving surgical treatment for endometriosis during laparoscopic surgery, and RNA-seq was used to examine differentially expressed genes (DEGs) in eutopic and ectopic endometrial stromal cells. The functional significance of the differentially expressed genes was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 1309 upregulated and 663 downregulated genes were identified through the analysis of the transcriptomes of eutopic and ectopic endometrial stromal cells. Furthermore, KEGG analysis indicated that these DEGs were mainly enriched in the PI3K-Akt signaling pathway, cytokine–cytokine receptor interaction, and MAPK signaling pathway. Our study identified differential gene expression in eutopic as compared to ectopic endometrial tissue stromal cells. We strongly believe that our findings can bring new insights into the underlying mechanisms of endometriosis. However, future research is necessary to clarify the roles of the identified genes. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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12 pages, 278 KiB  
Article
COBLL1 and IRS1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes
by Przemyslaw Ustianowski, Damian Malinowski, Michał Czerewaty, Krzysztof Safranow, Maciej Tarnowski, Violetta Dziedziejko and Andrzej Pawlik
Biomedicines 2022, 10(8), 1933; https://doi.org/10.3390/biomedicines10081933 - 9 Aug 2022
Cited by 3 | Viewed by 1559
Abstract
Gestational diabetes mellitus (GDM) is carbohydrate intolerance in pregnant women leading to various complications. Currently, there is a search for factors predisposing to GDM. Among them are genetic polymorphisms of genes involved in insulin secretion as well as carbohydrate metabolism. Due to the [...] Read more.
Gestational diabetes mellitus (GDM) is carbohydrate intolerance in pregnant women leading to various complications. Currently, there is a search for factors predisposing to GDM. Among them are genetic polymorphisms of genes involved in insulin secretion as well as carbohydrate metabolism. Due to the similar pathogenesis of GDM to type 2 diabetes (T2DM), genetic polymorphisms associated with T2DM are considered. The aim of this study was to examine the associations between the COBLL1 rs7607980 T > C and IRS1 rs2943641 T > C gene polymorphisms and the risk of GDM as well as selected clinical parameters in women with GDM. Additionally, we examined the expression of these genes in the placenta of women with and without GDM in correlation with selected clinical parameters. This study included 328 pregnant women with normal glucose tolerance (NGT) and 251 pregnant women with GDM diagnosed on the basis of a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation. There were no statistically significant differences in the distribution of IRS1 rs2943641 gene polymorphisms between women with GDM and pregnant women with NGT. In the GDM group, we observed a decreased frequency of COBLL1 rs7607980 CC homozygous women (CC vs. TC+TT, p = 0.048); however, there was no statistically significant difference in the frequency of alleles between women with GDM and the control group. There were no statistically significant associations between COBLL1 rs7607980 gene polymorphism and clinical parameters in women with GDM. In GDM women with the IRS1 rs2943641 TT genotype, fasting glucose levels were significantly higher than in women with CC and TC genotypes. There was no statistically significant difference in the expression of COBLL1 and IRS1 genes in the placenta between women with GDM and healthy women. There were no statistically significant correlations between COBLL1 gene expression in the placenta and clinical parameters. The expression of IRS1 correlated significantly with an increase in BMI during pregnancy. The results of this study suggest that COBLL1 rs7607980 and IRS1 rs2943641 gene polymorphisms are not significant risk factors for GDM in our population. The IRS1 TT genotype may be associated with higher fasting glucose levels in women with GDM. Expression of the IRS1 gene in the placenta positively correlates with an increase in BMI during pregnancy in women with GDM. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)

Review

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19 pages, 774 KiB  
Review
Molecular Mechanisms of Endometriosis Revealed Using Omics Data
by Seong Beom Cho
Biomedicines 2023, 11(8), 2210; https://doi.org/10.3390/biomedicines11082210 - 7 Aug 2023
Cited by 1 | Viewed by 1828
Abstract
Endometriosis is a gynecological disorder prevalent in women of reproductive age. The primary symptoms include dysmenorrhea, irregular menstruation, and infertility. However, the pathogenesis of endometriosis remains unclear. With the advent of high-throughput technologies, various omics experiments have been conducted to identify genes related [...] Read more.
Endometriosis is a gynecological disorder prevalent in women of reproductive age. The primary symptoms include dysmenorrhea, irregular menstruation, and infertility. However, the pathogenesis of endometriosis remains unclear. With the advent of high-throughput technologies, various omics experiments have been conducted to identify genes related to the pathophysiology of endometriosis. This review highlights the molecular mechanisms underlying endometriosis using omics. When genes identified in omics experiments were compared with endometriosis disease genes identified in independent studies, the number of overlapping genes was moderate. However, the characteristics of these genes were found to be equivalent when functional gene set enrichment analysis was performed using gene ontology and biological pathway information. These findings indicate that omics technology provides invaluable information regarding the pathophysiology of endometriosis. Moreover, the functional characteristics revealed using enrichment analysis provide important clues for discovering endometriosis disease genes in future research. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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23 pages, 2516 KiB  
Review
Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement
by Nicolas Monnin, Anne Julie Fattet and Isabelle Koscinski
Biomedicines 2023, 11(3), 978; https://doi.org/10.3390/biomedicines11030978 - 22 Mar 2023
Cited by 12 | Viewed by 4930
Abstract
Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source [...] Read more.
Endometriosis is a chronic disease caused by ectopic endometrial tissue. Endometriotic implants induce inflammation, leading to chronic pain and impaired fertility. Characterized by their dependence on estradiol (via estrogen receptor β (ESRβ)) and their resistance to progesterone, endometriotic implants produce their own source of estradiol through active aromatase. Steroidogenic factor-1 (SF1) is a key transcription factor that promotes aromatase synthesis. The expression of SF1 and ESRβ is enhanced by the demethylation of their promoter in progenitor cells of the female reproductive system. High local concentrations of estrogen are involved in the chronic inflammatory environment favoring the implantation and development of endometriotic implants. Similar local conditions can promote, directly and indirectly, the appearance and development of genital cancer. Recently, certain components of the microbiota have been identified as potentially promoting a high level of estrogen in the blood. Many environmental factors are also suspected of increasing the estrogen concentration, especially prenatal exposure to estrogen-like endocrine disruptors such as DES and bisphenol A. Phthalates are also suspected of promoting endometriosis but throughmeans other than binding to estradiol receptors. The impact of dioxin or tobacco seems to be more controversial. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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10 pages, 915 KiB  
Review
The Emerging Role of Menstrual-Blood-Derived Stem Cells in Endometriosis
by Mariana Robalo Cordeiro, Carlota Anjinho Carvalhos and Margarida Figueiredo-Dias
Biomedicines 2023, 11(1), 39; https://doi.org/10.3390/biomedicines11010039 - 24 Dec 2022
Cited by 7 | Viewed by 3798
Abstract
The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them [...] Read more.
The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them in the spotlight for endometriosis research. The stem cell theory for endometriosis pathogenesis, supported by the consensual mechanism of retrograde menstruation, highlights the recognized importance that MenSC have gained by potentially being directly related to the genesis, development and maintenance of ectopic endometriotic lesions. Meanwhile, the differences observed between MenSC in patients with endometriosis and in healthy women underlines the applicability of these cells as a putative biomarker for the early diagnosis of endometriosis, as well as for the development of targeted therapies. It is expected that in the near future MenSC will have the potential to change the way we manage this complex disease, once their long-term safety and effectiveness are assessed. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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18 pages, 2008 KiB  
Review
Impact of Adenomyosis on Infertile Patients—Therapy Options and Reproductive Outcomes
by Veronika Günther, Leila Allahqoli, Georgios Gitas, Nicolai Maass, Karolin Tesch, Johannes Ackermann, Paula Rosam, Liselotte Mettler, Sören von Otte and Ibrahim Alkatout
Biomedicines 2022, 10(12), 3245; https://doi.org/10.3390/biomedicines10123245 - 13 Dec 2022
Cited by 4 | Viewed by 5636
Abstract
Adenomyosis is associated with a negative impact on reproductive outcomes. Although adenomyosis is detected more frequently in women of late reproductive age, its impact on pregnancy rates is important because, in today’s world, family planning has shifted towards the late reproductive phase of [...] Read more.
Adenomyosis is associated with a negative impact on reproductive outcomes. Although adenomyosis is detected more frequently in women of late reproductive age, its impact on pregnancy rates is important because, in today’s world, family planning has shifted towards the late reproductive phase of life for many women. Although the diagnostic indications for imaging studies are well-known, we lack strict diagnostic criteria and classification systems concerning the extent of the disease. Selecting the optimal evidence-based treatment option for adenomyosis is difficult because of the paucity of evidence concerning the association between fertility and the degree and composition of adenomyosis. Furthermore, the treatment of infertility might interfere with the treatment of adenomyosis due to the presence of pain. The aim of this review is to analyze the association between adenomyosis and infertility, and describe treatment options to enhance reproductive outcomes. The following aspects will be addressed in detail: (a) prevalence and causes of adenomyosis, (b) diagnostic tools with imaging techniques, (c) clinical symptoms, (d) proposed pathomechanism of adenomyosis and infertility, and (e) different treatment approaches (pharmacological, surgical, others) and their impact on reproductive outcomes. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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12 pages, 1432 KiB  
Review
MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis
by Fahimeh Ghasemi, Effat Alemzadeh, Leila Allahqoli, Esmat Alemzadeh, Afrooz Mazidimoradi, Hamid Salehiniya and Ibrahim Alkatout
Biomedicines 2022, 10(10), 2558; https://doi.org/10.3390/biomedicines10102558 - 13 Oct 2022
Cited by 4 | Viewed by 1882
Abstract
Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a [...] Read more.
Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient’s quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 3.0)
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