Endometriosis Treatment Report
www.EndometriosisTreatmentReport.com
https://www.dailymail.co.uk/health/article-8808029/Experts-believe-time-radical-rethink-endometriosis-treated.html
Can surgery for a monthly misery make it worse? It affects thousands of women, but now some experts believe it’s time for a radical rethink of how endometriosis is treated
Experts believe it’s time for a radical rethink of how endometriosis is treated
https://www.pnas.org/content/early/2020/09/29/1920037117
https://www.ncbi.nlm.nih.gov/pubmed/33004630?dopt=Abstract
Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis.
Proc Natl Acad Sci U S A. 2020 Oct 01;:
Authors: Li WN, Hsiao KY, Wang CA, Chang N, Hsu PL, Sun CH, Wu SR, Wu MH, Tsai SJ
Abstract
Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic regimens. Herein, we identified that vascular endothelial growth factor (VEGF)-C, a potent lymphangiogenic factor, is up-regulated in endometriotic cells and contributes to increased lymphangiogenesis. Bioinformatic analysis and molecular biological characterization revealed that VEGF-C is negatively regulated by an orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII). Further studies demonstrated that proinflammatory cytokines, via suppression of COUP-TFII level, induce VEGF-C overexpression. More importantly, we show that functional VEGF-C is transported by extracellular vesicles (EVs) to enhance the lymphangiogenic ability of lymphatic endothelial cells. Autotransplanted mouse model of endometriosis showed lenvatinib treatment abrogated the increased lymphatic vessels development in the endometriotic lesion, enlarged retroperitoneal lymph nodes, and immune cells infiltration, indicating that blocking VEGF-C signaling can reduce local chronic inflammation and concomitantly endometriosis development. Evaluation of EV-transmitted VEGF-C from patients’ sera demonstrates it is a reliable noninvasive way for clinical diagnosis. Taken together, we identify the vicious cycle of inflammation, COUP-TFII, VEGF-C, and lymphangiogenesis in the endometriotic microenvironment, which opens up new horizons in understanding the pathophysiology of endometriosis. VEGF-C not only can serve as a diagnostic biomarker but also a molecular target for developing therapeutic regimens.
PMID: 33004630 [PubMed – as supplied by publisher]
https://www.mdpi.com/2075-4418/10/10/771/htm
https://www.ncbi.nlm.nih.gov/pubmed/33007875?dopt=Abstract
Endometriosis and the Urinary Tract: From Diagnosis to Surgical Treatment.
Diagnostics (Basel). 2020 Sep 30;10(10):
Authors: Leonardi M, Espada M, Kho RM, Magrina JF, Millischer AE, Savelli L, Condous G
Abstract
We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools, including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team for complex cases that involve the urinary tract. While bladder deep endometriosis (DE) is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE, due to the serious health implications for women. When UTE exists, it is important to work within an interdisciplinary radiological and surgical team.
PMID: 33007875 [PubMed – as supplied by publisher]
https://www.minervamedica.it/en/journals/minerva-ginecologica/article.php?cod=R09Y9999N00A20091401
https://www.ncbi.nlm.nih.gov/pubmed/32921020?dopt=Abstract
Effectiveness of the integration of quercetin, turmeric, and N-acetylcysteine in reducing inflammation and pain associated with endometriosis. In vitro and in vivo studies.
Minerva Ginecol. 2020 Sep 14;:
Authors: Fadin M, Nicoletti MC, Pellizzato M, Accardi M, Baiett MG
Abstract
OBJECTIVE: To evaluate the efficacy of oral administration of a novel composition composed of Quercetin, Curcumin, Acetylcysteine in reducing pain in women affected by endometriosis, through the reduction of the inflammatory-hyperproliferative component of the ectopic endometrial tissue.
METHODS: 33 women with clinical diagnosis of endometriosis from at least 3 months have been enrolled. Patients have been treated daily with 200 mg of Quercetin, 210 mg of dry extract of Curcuma Longa (titrated at 95% in Curcuminoids) and 150 mg of Acetylcysteine (1 tablet of Alliendo) for 2 months. The overall symptomatology with specific reference to dysmenorrhea, pelvic pain and dyspareunia, together with the frequency of NSAID’s drugs assumption have been evaluated at the beginning and at the end of the treatment.
RESULTS: Overall, the results collected at the end of the treatment according to the parameters evaluated and above mentioned on the 33 patients enrolled, show a significative improvement in the reduction of pain symptoms associated to endometriosis (p<0,001 for dysmenorrhea, pelvic pain and dyspareunia). The use of NSAID's together with an overall reduction of their dosage and time of assumption has been reduced as well. No significative side effects have been observed. CONCLUSIONS: The aforementioned results suggest that administration of the composition described can represent a valuable adjuvant treatment in the reduction of pain symptomatology associated to endometriosis, triggered by inflammatory cascade and hyperproliferation of ectopic tissue. PMID: 32921020 [PubMed - as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03840993?type=Intr&cond=Endometriosis&lupd_s=08%2F31%2F2020&lupd_d=14
Condition : Endometrial Related Pain
Interventions : Drug: MT-2990; Drug: Placebo
Sponsor : Mitsubishi Tanabe Pharma Development America, Inc.
Recruiting
Safety and Efficacy Study of MT-2990 in Women With Endometriosis
NCT03840993
Fri, 15 Feb 2019 12:00:00 EST
Last Update Posted: 09/14/20 07:13AM
https://www.dovepress.com/emodin-reverses-the-epithelialndashmesenchymal-transition-of-human-end-peer-reviewed-fulltext-article-DDDT
https://www.ncbi.nlm.nih.gov/pubmed/32982173?dopt=Abstract
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490435/
Related Articles
Emodin Reverses the Epithelial-Mesenchymal Transition of Human Endometrial Stromal Cells by Inhibiting ILK/GSK-3β Pathway.
Drug Des Devel Ther. 2020;14:3663-3672
Authors: Zheng Q, Wang J, Li W, Chen X, Chen S, Chen L
Abstract
Purpose: To explore the exact mechanism through which emodin down-regulates the migration and invasion abilities of endometrial stromal cells. Moreover, to explore the theoretical basis of emodin in the treatment of endometriosis.
Patients and Methods: Endometriosis endometrial stromal cells (EESs) were cultured from 15 women with endometriosis and control endometrial stromal cells (CESs) were cultured from 12 women without endometriosis. The levels of proteins were evaluated by Western blot. The migration and invasion abilities of cells were detected by transwell assays.
Results: The abilities of migration and invasion of EESs were much stronger than those of CESs. After treated with emodin, the migration and invasion abilities of EESs and CESs were significantly down-regulated, and the levels of integrin-linked kinase (ILK) and p-GSK-3β were statistically down-regulated in EESs. Besides that, the expression of keratin was up-regulated while the expression of vimentin, β-catenin and slug were all down-regulated by emodin in a dose- and time-dependent manner. Silencing of ILK gene in EESs also achieved the above effects, which were strengthened by emodin. Conversely, exogenous expression of ILK in CESs increased the expression of p-GSK-3β, which were abrogated by emodin. Furthermore, SB216763 increased migration and invasion abilities of CESs by facilitating the epithelial-mesenchymal transition (EMT) through up-regulating levels of p-GSK-3β, β-catenin and slug, which were also abrogated by emodin.
Conclusion: Emodin inhibits the migration and invasion abilities of human endometrial stromal cells by reversing the EMT via ILK/GSK-3β pathway. So, emodin may be considered as a promising targeted therapy for endometriosis.
PMID: 32982173 [PubMed – in process]
https://www.endonews.com/endometrium-and-hoxa-10-gene
Endometrium and HOXA 10 gene
https://www.endonews.com/new-rat-model-of-endometriosis-could-help-researchers-develop-new-treatments-for-the-condition
New Rat Model of Endometriosis Could Help Researchers Develop New Treatments for the Condition
https://clinicaltrials.gov/ct2/show/NCT03633786?type=Intr&cond=Endometriosis&lupd_s=07%2F29%2F2020&lupd_d=14
Condition : Endometriosis
Interventions : Procedure: standard laparoscopic surgery; Procedure: robot-assisted surgery; Diagnostic Test: assessment of sexual function; Diagnostic Test: assessment of bowel symptoms; Diagnostic Test: assessment of urinary symptoms
Sponsor : Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Recruiting
Robot-assisted Versus Standard Laparoscopic Approach for the Surgical Treatment of Deep Infiltrating Endometriosis
NCT03633786
Thu, 16 Aug 2018 12:00:00 EDT
Last Update Posted: 08/12/20 07:18AM
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01856-8
https://pubmed.ncbi.nlm.nih.gov/32771033/
https://www.ncbi.nlm.nih.gov/pubmed/32771033?dopt=Abstract
Biological characteristics of endometriotic mesenchymal stem cells isolated from ectopic lesions of patients with endometriosis.
Stem Cell Res Ther. 2020 Aug 08;11(1):346
Authors: Liu Y, Liang S, Yang F, Sun Y, Niu L, Ren Y, Wang H, He Y, Du J, Yang J, Lin J
Abstract
BACKGROUND: Research into the pathogenesis of endometriosis (EMs) would substantially promote its effective treatment and early diagnosis. However, the aetiology of EMs is poorly understood and controversial despite the progress in EMs research in the last several decades. Currently, accumulating evidence has shed light on the importance of endometrial stem cells (EnSCs) residing in the basal layer of endometrium in the establishment and progression of endometriotic lesions. Therefore, we aimed to identify the differences between EnSCs isolated from the ectopic lesions of EMs patients (EnSC-EM-EC) and EnSCs isolated from eutopic endometrium of control group (EnSC-Control). We further performed preliminary exploration of the potential signalling pathways involved in the above abnormalities.
METHODS: EnSC-EM-EC (n = 12) and EnSC-Control (n = 13) were successfully isolated. Then, the proliferative capacity, migratory capacity and angiogenic potential of EnSCs were evaluated by conventional MTT assay, flow cytometry, wound healing assay, transwell assay, tube formation assay and chick embryo chorioallantoic membrane assay respectively. The expression of 11 angiogenesis-associated biological factors and 11 cytokines secreted by EnSCs and 17 adhesion molecules expressed on EnSCs were determined by protein array assays respectively. Differentially expressed genes (DEGs) between EnSC-EM-EC and EnSC-Control were analysed by RNA-sequence.
RESULTS: EnSC-EM-EC exhibited unique biological characteristics, including prolonged mitosis, enhanced migratory capacity and enhanced angiogenic potential. Greater amounts of angiogenic factors (especially VEGF and PDGF) were secreted by EnSC-EM-EC than by EnSC-Control; however, the distinct profiles of cytokines secreted by EnSC-EM-EC and adhesion molecules expressed by EnSC-EM-EC require further investigation. A total of 523 DEGs between EnSC-EM-EC and EnSC-Control were identified and analysed using the KEGG and Gene Ontology databases.
CONCLUSIONS: Our results not only improve the understanding of EMs but also contribute to the development of EnSC-EM-EC as a tool for EMs drug discovery. These cells could be of great help in exploiting promising therapeutic targets and new biomarkers for EMs treatment and prognosis.
PMID: 32771033 [PubMed – in process]
https://www.sciencedirect.com/science/article/abs/pii/S0022399920307753?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32781264?dopt=Abstract
Partners’ perspective in endometriosis research and treatment: A systematic review of qualitative and quantitative evidence.
J Psychosom Res. 2020 Aug 06;137:110213
Authors: Facchin F, Buggio L, Saita E
Abstract
OBJECTIVE: To summarize the available qualitative and quantitative evidence regarding the impact of endometriosis on women’s partners.
METHODS: A systematic electronic search of PubMed and PsycINFO was conducted. All the available evidence regarding partners’ psychological condition, quality of life, social and intimate relationships, and sexuality was included, and a narrative synthesis of the findings was provided.
RESULTS: Of 127 studies retrieved through electronic search, only 5 (3 qualitative/semi-qualitative and 2 quantitative studies) matched the inclusion criteria and were included in our review. In total, participants were 399 male partners. Endometriosis negatively affects partners’ psychological wellbeing and quality of life, with significant individual differences. Partners of women with endometriosis may experience isolation and lack of engagement in treatment decision-making. Partners also experience the economic burden of the disease, with negative consequences on work functioning and daily life. Sexuality is also negatively affected, although with contradictory findings. Positive aspects of personal and relationship growth were also reported.
CONCLUSION: Endometriosis is an important cause of physical and psychological pain for women, but it may also have a negative impact on their partners. Although the effects of other chronic diseases on partners and caregivers have been largely explored, the small number of articles included in this review indicates that this topic remains understudied in endometriosis research. Endometriosis should be investigated and managed within a systemic framework, with a specific focus on the complex dynamic interaction between individual, relational, sociocultural and environmental factors.
PMID: 32781264 [PubMed – as supplied by publisher]
https://www.sciencealert.com/how-common-treatments-for-endometriosis-are-failing-those-with-chronic-pain
How Common Treatments For Endometriosis Are Failing Those With Chronic Pain
https://www.endofound.org/u.s.-house-approves-doubling-funding-for-endometriosis-research-to-26-million-annually
https://www.mdpi.com/2077-0383/9/8/2461
https://www.ncbi.nlm.nih.gov/pubmed/32752110?dopt=Abstract
Related Articles
Long-Term Evolution of Quality of Life and Symptoms Following Surgical Treatment for Endometriosis: Different Trajectories for Which Patients?
J Clin Med. 2020 Jul 31;9(8):
Authors: Comptour A, Lambert C, Chauvet P, Figuier C, Gremeau AS, Canis M, Pereira B, Bourdel N
Abstract
Many studies have shown a global efficacy of laparoscopic surgery for patients with endometriosis in reducing painful symptoms and improving quality of life (QoL) in the short and long-term. The aim of this study was to analyze the different trajectories of long-term evolution in QoL and symptoms following surgical treatment for endometriosis, and to identify corresponding patient profiles. This prospective and multicenter cohort study concerned 962 patients who underwent laparoscopic treatment for endometriosis. QoL was evaluated using the Short Form (SF)-36 questionnaire and intensity of pain was reported using a visual analog scale prior to surgery and at 6, 12, 18, 24 and 36 months after surgery. Distinctive trajectories of pain and QoL evolution were identified using group-based trajectory modeling, an approach which gathers individuals into meaningful subgroups with statistically similar trajectories. Pelvic symptom trajectories (models of the evolution of dysmenorrhea, dyspareunia and chronic pelvic pain intensity over years) correspond to (1) patients with no pain or pain no longer after surgery, (2) patients with the biggest improvement in pain and (3) patients with continued severe pain after surgery. Our study reveals clear trajectories for the progression of symptoms and QoL after surgery that correspond to clusters of patients. This information may serve to complete information obtained from epidemiological methods currently used in selecting patients eligible for surgery.
PMID: 32752110 [PubMed]
https://www.birpublications.org/doi/10.1259/bjr.20200690
https://www.ncbi.nlm.nih.gov/pubmed/32706984?dopt=Abstract
Related Articles
MRI for the diagnosis and staging of deeply infiltrating endometriosis: a national survey of BSGE accredited endometriosis centres and review of the literature.
Br J Radiol. 2020 Oct 01;93(1114):20200690
Authors: Wild M, Pandhi S, Rendle J, Swift I, Ofuasia E
Abstract
OBJECTIVES: Our objective was to establish the primary mode of imaging and MR protocols utilised in the preoperative staging of deeply infiltrating endometriosis in centres accredited by the British Society of Gynaecological Endoscopy (BSGE).
METHODS: The lead consultant radiologist in each centre was invited to complete an online survey detailing their protocols.
RESULTS: Out of 49 centres, 32 (65%) responded to the survey. Two centres performed transvaginal ultrasound as the primary method for preoperative staging of deeply infiltrating endometriosis and the remainder performed MRI. 21/25 centres did not recommend a period of fasting prior to MRI and 22/25 administered hyoscine butylbromide. None of the centres routinely offered bowel preparation or recommended a specific pre-procedure diet. 21/25 centres did not time imaging according to the woman’s menstrual cycle, and instructions regarding bladder filling were varied. Rectal and vaginal opacification methods were infrequently utilised. All centres preferentially performed MRI in the supine position – six used an abdominal strap and four could facilitate prone imaging. Just under half of centres used pelvic-phased array coils and three centres used gadolinium contrast agents routinely. All centres performed T1W with fat-suppression and T2W without fat-suppression sequences. There was significant variation relating to other MR sequences depending on the unit.
CONCLUSIONS: There was significant inconsistency between centres in terms of MR protocols, patient preparation and the sequences performed. Many practices were out of line with current published evidence.
ADVANCES IN KNOWLEDGE: Our survey demonstrates a need for evidence-based standardisation of imaging in BSGE accredited endometriosis centres.
PMID: 32706984 [PubMed – indexed for MEDLINE]
https://clinicaltrials.gov/ct2/show/NCT04493476?type=Intr
https://clinicaltrials.gov/ct2/show/NCT04493476?type=Intr&cond=Endometriosis&lupd_s=07%2F16%2F2020&lupd_d=14
Condition : Endometriosis
Intervention : Drug: Chinese herbal formula
Sponsor : Carmel Medical Center
Not yet recruiting
Using a Herbal Remedy Extract for the Treatment of Endometriosis Symptoms
NCT04493476
Thu, 30 Jul 2020 12:00:00 EDT
Last Update Posted: 07/30/20 07:09AM
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397419/
https://www.hindawi.com/journals/ecam/2020/8521831/
https://www.ncbi.nlm.nih.gov/pubmed/32774432?dopt=Abstract
The Ethanol Extract of Avocado (Persea americana Mill. (Lauraceae)) Seeds Successfully Induces Implant Regression and Restores Ovarian Dynamic in a Rat Model of Endometriosis.
Evid Based Complement Alternat Med. 2020;2020:8521831
Authors: Minko Essono S, Mvondo MA, Ngadjui E, Kemka Nguimatio FX, Watcho P
Abstract
Endometriosis is an estrogen-dependent disease with conventional therapies which do not have desirable effectiveness and possess many side effects. Scientific evidences suggest that medicinal plants with antioxidant, anti-inflammatory, and/or antiproliferative properties are potential alternatives for the treatment of endometriosis. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro and in vivo. This study therefore is aimed at investigating the effects of such an extract on an experimental model of endometriosis. Endometriosis was induced by grafting uterine fragments onto the peritoneum of female Wistar rats. After checking the success of the transplantation surgery, animals with endometriosis were orally treated with the ethanol extract of P. americana seeds at the doses of 12.5, 25, and 50 mg/kg. The positive control was treated with letrozole (10 mg/kg) while the negative control received the vehicle. Treatments lasted 7 days and animals were sacrificed thereafter. Endometrial implant volume was determined. Estradiol and progesterone levels were measured in serum samples and endometriosis lesions. The oxidative status of endometriosis lesions was evaluated. Histological analysis of endometriosis lesions, uterus, and ovaries was also performed. Results showed that the ethanol extract of P. americana seeds decreased endometrial implant volume (p < 0.001) and serum levels of estradiol and progesterone (p < 0.01). The levels of estradiol also decreased in endometriosis lesions at doses of 12.5 and 50 mg/kg (p < 0.001). Both malondialdehyde and glutathione levels increased in endometriosis lesions (p < 0.001). The ectopic endometrium height decreased and the number of antral follicles and corpora lutea (p < 0.05) increased while that of luteinized unruptured follicles decreased (p < 0.001). In conclusion, the ethanol extract of P. americana seeds displayed an antiendometriosis effect suggesting that it could be a potential alternative for the treatment of endometriosis. PMID: 32774432 [PubMed - as supplied by publisher]
https://link.springer.com/article/10.1007%2Fs43032-020-00226-2
https://www.ncbi.nlm.nih.gov/pubmed/32700282?dopt=Abstract
Related Articles
Epigenetics of Estrogen and Progesterone Receptors in Endometriosis.
Reprod Sci. 2020 Jul 22;:
Authors: Chen H, Malentacchi F, Fambrini M, Harrath AH, Huang H, Petraglia F
Abstract
Endometriosis is an estrogen-dependent inflammatory gynecological disease. Increased estrogen activity and progesterone resistance are the main hormonal substrate of this disease and are associated with inflammatory response and debilitating symptoms, including pain and infertility. Estrogens and progesterone act via their specific nuclear receptors. The regulation of receptor expression by epigenetics maybe a critical factor for endometriosis. The present review aims to discuss the epigenetic mechanisms related to the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in patients with endometriosis, including two classic epigenetic mechanisms: DNA methylation and histone modification, and, other non-classic mechanisms: miRNAs and lncRNA. Several in vitro and in vivo studies support the key role of epigenetics in the regulation of the expression of ERs and PRs, which may provide new molecules and targets for the diagnosis and treatment of endometriosis.
PMID: 32700282 [PubMed – as supplied by publisher]
https://www.frontiersin.org/articles/10.3389/frph.2020.00003/full
ORIGINAL RESEARCH ARTICLE
Front. Reprod. Health, 22 July 2020 | https://doi.org/10.3389/frph.2020.00003
Menstrual Effluent Provides a Novel Diagnostic Window on the Pathogenesis of Endometriosis
https://academic.oup.com/biolreprod/article-abstract/doi/10.1093/biolre/ioaa126/5874328?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/32697296?dopt=Abstract
Related Articles
Fibrinogen alpha chain (FGA) promotes the migration and invasion of human endometrial stromal cells in endometriosis through FAK/AKT/MMP-2 pathway†.
Biol Reprod. 2020 Jul 22;:
Authors: Li H, Ma RQ, Cheng HY, Ye X, Zhu HL, Chang XH
Abstract
Fibrinogen alpha chain (FGA), a cell adhesion molecule, contains two arginyl-glycyl-aspartic acid (RGD) cell adhesion sequences. Our previous study demonstrated that FGA, as an up-regulated protein in endometriosis (EM), was closely related to disease severity and involved in the development of EM. However, the biological functional and underlying mechanism of FGA in EM have not been fully understood. To explore the roles of FGA in EM, we analyzed the effects of FGA on the biological behaviors of human primary eutopic endometrial stromal cells (EuESC). The results indicated FGA knockdown suppressed the migration and invasion ability of EuESC, which also altered the distribution of cytoskeletal filamentous and cell morphology. Western blot analysis demonstrated that knockdown of FGA attenuated the migration-related protein levels of vimentin and MMP-2, but not integrin subunit alpha V (ITGAV), integrin subunit beta 3 (ITGB3). Meanwhile, integrin-linked transduction pathways were detected. We found FGA knockdown significantly suppressed the expression of FAK level and AKT phosphorylation, without ERK dependent pathways. Treatment with the AKT inhibitor MK2206 or RGD antagonist highly decreased the effects of FGA on the migration and invasion of EuESC. RGD antagonist treatment strongly inhibited FAK and AKT dependent pathways, but not ERK pathways. Our data indicated that FGA may enhance the migration and invasion of EuESC through RGD sequences binding integrin and activating the FAK/AKT/MMP-2 signaling pathway. This novel finding suggests that FGA may provide a novel potential approach to the treatment of EM, which provides a new way to understand the pathogenesis of endometriosis.
PMID: 32697296 [PubMed – as supplied by publisher]
https://www.northwell.edu/news/the-latest/endometriosis-research-provides-new-origin-clues-potential-diagnostic-and-possible-treatment-avenues
https://www.businesswire.com/news/home/20200722005534/en/Endometriosis-Research-New-Origin-Clues-Potential-Diagnostic
Endometriosis Research Provides New Origin Clues, Potential Diagnostic and Possible Treatment Avenues
Feinstein Institutes researchers expand menstrual effluent study to better understand the complex disorder of endometriosis
https://clinicaltrials.gov/ct2/show/NCT03430609?type=Intr
https://clinicaltrials.gov/ct2/show/NCT03430609?type=Intr&cond=Endometriosis&lupd_s=07%2F08%2F2020&lupd_d=14
Conditions : Endometriosis Ovary; Laparoscopy; Ovary; Functional Disturbance; Hemostasis
Interventions : Procedure: Laparoscopic treatment for endometrioma Astus©; Diagnostic Test: AMH Level; Diagnostic Test: Transvaginal ultrasound for antral follicle count; Procedure: Laparoscopic treatment for endometrioma Vicryl®; Procedure: Laparoscopic treatment for endometrioma Surgicel®
Sponsors : Faculdade de Ciências Médicas da Santa Casa de São Paulo; Federal University of Paraíba; Irmandade da Santa Casa de Misericordia de Sao Paulo
Active, not recruiting
Ovarian Function After Use of Various Hemostatic Techniques During Treatment for Endometrioma
NCT03430609
Tue, 13 Feb 2018 12:00:00 EST
Last Update Posted: 07/22/20 08:20AM
https://clinicaltrials.gov/ct2/show/NCT01942122?type=Intr
https://clinicaltrials.gov/ct2/show/NCT01942122?type=Intr&cond=Endometriosis&lupd_s=07%2F08%2F2020&lupd_d=14
Conditions : Endometrioma; Visual Analogue Pain Scale: Moderate or Severe Pain
Interventions : Drug: DLBS1442 100; Drug: Mefenamic acid; Drug: DLBS1442 200
Sponsor : Dexa Medica Group
Recruiting
DLBS1442 for The Treatment of Pain in Patients Suspected Endometriosis
NCT01942122
Fri, 13 Sep 2013 12:00:00 EDT
Last Update Posted: 07/22/20 08:19AM
https://link.springer.com/article/10.1007%2Fs11596-020-2213-1
https://www.ncbi.nlm.nih.gov/pubmed/32681259?dopt=Abstract
Related Articles
The Role of Ankaferd Blood Stopper and Oxytocin as Potential Therapeutic Agents in Endometriosis: A Rat Model.
Curr Med Sci. 2020 Jun;40(3):556-562
Authors: Hortu I, Ozceltik G, Karadadas E, Erbas O, Yigitturk G, Ulukus M
Abstract
To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis. PMID: 32681259 [PubMed - as supplied by publisher]
https://www.sciencedirect.com/science/article/pii/S0753332220306697?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32768961?dopt=Abstract
Related Articles
Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1.
Biomed Pharmacother. 2020 Jul 08;129:110476
Authors: Li T, Wang J, Guo X, Yu Q, Ding S, Xu X, Peng Y, Zhu L, Zou G, Zhang X
Abstract
BACKGROUND: The density and the activity of mast cells are associated with endometriosis. However, the role of mast cells on the pathogenesis of endometriosis remains unclear. Our study aims to investigate whether endometrial cells interact with mast cells and the involvement of their crosstalk in the development of endometriosis.
METHODS: The transwell assay was applied to investigate the effect of mast cells on the migratory ability of human primary endometrial cells. Mast cells were cocultured with endometrial epithelial and stromal cells respectively and total RNAs were isolated and subjected to mRNA sequencing. Next, the transwell assay, CCK-8, and tube formation were applied to study the role of CCL8 on the endometrial and endothelial cells in vitro. The mouse model was also established to confirm the role of CCL8 in the development and angiogenesis of endometriosis.
RESULTS: CCL8 was up-regulated in mast cells when cocultured with endometrial cells. CCL8 was highly expressed in the ectopic endometrium and the serum of patients with endometriosis. CCL8 promoted the migratory ability of endometrial epithelial and stromal cells and increased the proliferation, migration, and tube formation of endothelial cells. CCR1, the receptor of CCL8, was over-expressed in the ectopic endometrium and colocalized with blood vessels in ovarian endometriomas. The inhibition of CCR1 suppressed the development and angiogenesis of endometriosis in vivo.
CONCLUSION: The crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1 was demonstrated, thereby providing a new treatment strategy for endometriosis.
PMID: 32768961 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04452123?type=Intr
https://clinicaltrials.gov/ct2/show/NCT04452123?type=Intr&cond=Endometriosis&lupd_s=06%2F16%2F2020&lupd_d=14
Condition : Endometrioma
Interventions : Procedure: Laparoscopic argon plasma treatment of endometrioma; Procedure: Laparoscopic stripping of endometrioma and suture/coagulation of the rest of ovary
Sponsor : Charles University, Czech Republic
Not yet recruiting
Endometrioma Treatment and Ovarian Function
NCT04452123
Tue, 30 Jun 2020 12:00:00 EDT
Last Update Posted: 06/30/20 07:27AM
https://clinicaltrials.gov/ct2/show/NCT04445025?type=Intr
https://clinicaltrials.gov/ct2/show/NCT04445025?type=Intr&cond=Endometriosis&lupd_s=06%2F10%2F2020&lupd_d=14
Conditions : Infertility; Endometriosis
Interventions : Drug: Elagolix 200 MG; Drug: Leuprolide Acetate 3.75 MG/ML; Diagnostic Test: Lab work
Sponsors : Colorado Center for Reproductive Medicine; AbbVie
Not yet recruiting
Comparison Elagolix vs Depot Leuprolide Prior to Frozen Embryo Transfers in Patients With Endometriosis
NCT04445025
Wed, 24 Jun 2020 12:00:00 EDT
Last Update Posted: 06/24/20 07:14AM
Nanomedicine offers hope in battling endometriosis
https://www.nih.gov/news-events/news-releases/nih-funded-study-links-endometriosis-dna-changes
NIH-funded study links endometriosis to DNA changes
https://www.clinicalomics.com/topics/translational-research/epigenetics/epigenetic-changes-in-reproductive-cells-could-help-diagnose-endometriosis/
Epigenetic Changes in Reproductive Cells Could Help Diagnose Endometriosis
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008601
Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis
https://clinicaltrials.gov/ct2/show/NCT04417972?type=Intr&cond=Endometriosis&lupd_s=05%2F22%2F2020&lupd_d=14
Condition : Endometriosis
Interventions : Drug: SHR7280; Drug: Placebo oral tablet
Sponsor : Jiangsu HengRui Medicine Co., Ltd.
Not yet recruiting
The Pharmacokinetic(PK)/Pharmacodynamics(PD) Study of SHR7280 Tablets in Premenopausal Subjects With Endometriosis.
NCT04417972
Fri, 05 Jun 2020 12:00:00 EDT
Last Update Posted: 06/05/20 06:42AM
https://www.ajog.org/article/S0002-9378(20)30238-6/fulltext
https://www.ajog.org/article/S0002-9378(20)30238-6/pdf
https://www.ncbi.nlm.nih.gov/pubmed/32142827?dopt=Abstract
Related Articles
Research priorities for endometriosis differ among patients, clinicians, and researchers.
Am J Obstet Gynecol. 2020 06;222(6):630-632
Authors: Brady PC, Horne AW, Saunders PTK, Thomas AM, Missmer SA, Farland LV
PMID: 32142827 [PubMed – indexed for MEDLINE]
https://www.sciencedirect.com/science/article/abs/pii/S0944711320300465?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32736296?dopt=Abstract
The effects of isoliquiritigenin on endometriosis in vivo and in vitro study.
Phytomedicine. 2020 May 31;77:153214
Authors: Hsu YW, Chen HY, Chiang YF, Chang LC, Lin PH, Hsia SM
Abstract
BACKGROUND: Endometriosis is a common gynaecological disease characterized by growth of uterine endometrial tissue, outside the uterine cavity, on the ovaries, oviduct and pelvic peritoneum. Isoliquiritigenin (ISL) is a natural flavonoid isolated from the root of licorice (Glycyrrhiza uralensis) and shallot (Allium cepa). ISL has previously shown antioxidant, anti-inflammatory, anti-proliferation and anti-tumor activities.
PURPOSE: This study aimed to investigate the effects of ISL on endometriosis in vivo and in vitro.
METHODS: End1/E6E7 endometriosis cells were treated with ISL and β-estradiol. The MTT assay was used to detect cell viability. Cell migration was evaluated by the wound-healing assay. The expression of epithelial-to-mesenchymal transition (EMT)-related proteins were detected by western blot. Female Balb/c mice, surgically induced to have endometriosis by transplanting uterine tissue into the abdominal cavity, were treated with ISL or vehicle for 4 weeks. Lesion growth was subsequently analyzed by high-resolution ultrasound imaging. Serum and lesion inflammatory cytokines were measured by ELISA. EMT-related proteins and apoptosis-related proteins of endometriotic lesions were detected by western blot.
RESULTS: It was observed that ISL treatment inhibited the viability and migration of End1/E6E7. ISL treatment increased the expression of E-cadherin, and decreased the expression of N-cadherin, Slug and Snail. In the animal model, ISL treatment reduced the volume and weight of endometriotic lesions, decreased serum and lesion inflammatory cytokines, inhibited EMT, and induced apoptosis of the lesions.
CONCLUSION: ISL inhibited the viability, migration and EMT-related proteins of End1/E6E7 cells, reduced the volume and weight of endometriotic lesions, inhibited inflammatory cytokines and EMT, and induced apoptosis of the lesions to improve endometriosis.
PMID: 32736296 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04374006?type=Intr&cond=Endometriosis&lupd_s=04%2F21%2F2020&lupd_d=14
Conditions : Endometriosis; Peritoneum; Endometriosis
Interventions : Drug: Dienogest; Drug: Propolis; Other: placebo
Sponsor : Indonesia University
Active, not recruiting
Effects of Sulawesi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue
NCT04374006
Tue, 05 May 2020 12:00:00 EDT
Last Update Posted: 05/05/20 06:42AM
https://clinicaltrials.gov/ct2/show/NCT03986944?type=Intr
https://clinicaltrials.gov/ct2/show/NCT03986944?type=Intr&cond=Endometriosis&lupd_s=04%2F17%2F2020&lupd_d=14
Condition : Endometriosis
Interventions : Drug: 75 mg linzagolix tablet; Drug: 200 mg linzagolix tablet; Drug: Add-back capsule (E2 1 mg / NETA 0.5 mg); Drug: Placebo tablet to match 75 mg linzagolix tablet; Drug: Placebo tablet to match 200 mg linzagolix tablet; Drug: Placebo capsule to match Add-back capsule
Sponsor : ObsEva SA
Recruiting
A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat Endometriosis-associated Pain
NCT03986944
Fri, 14 Jun 2019 12:00:00 EDT
Last Update Posted: 05/01/20 08:08AM
https://clinicaltrials.gov/ct2/show/NCT03376451?type=Intr&cond=Endometriosis&lupd_s=04%2F14%2F2020&lupd_d=14
Conditions : Endometriosis (Diagnosis); Blood Biomarkers; Endometrium Biomarkers
Intervention : Other: Assessment of endometrium and blood biomarkers for endometriosis diagnosis
Sponsor : Dr Afchine Fazel
Recruiting
EndoSearch : Endometriosis Biomarkers
NCT03376451
Mon, 18 Dec 2017 12:00:00 EST
Last Update Posted: 04/28/20 06:55AM
https://www.forbes.com/sites/alicebroster/2020/04/26/relugolix-combination-therapy-may-be-the-way-to-cope-with-endometriosis-symptoms/#3d16c820589e
Relugolix Combination Therapy May Be The Way To Cope With Endometriosis Symptoms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379146/
https://www.ncbi.nlm.nih.gov/pubmed/32715291?dopt=Abstract
Related Articles
Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy.
Eur J Obstet Gynecol Reprod Biol X. 2020 Jul;7:100108
Authors: Maeda E, Koshiba A, Mori T, Ito F, Kataoka H, Okimura H, Sugahara T, Tarumi Y, Kusuki I, Khan KN, Kitawaki J
Abstract
Objective: Chronic inflammation in endometriosis is associated with increased risk of future cardiovascular disease; however, no studies have investigated the cardiovascular risk of women who have undergone hormonal therapy for endometriosis. We investigated atherosclerosis-related biomarkers in women with and without endometriosis and the effects of dienogest (DNG) and oral contraceptive (OC) therapies.
Study design: In this cross-sectional study, 109 women with endometriosis and 42 control women without endometriosis were enrolled. The endometriosis group was divided into the untreated (n = 34), DNG therapy (n = 33), and OC therapy (n = 42) groups. Lipid profile serum levels, inflammatory marker such as high-sensitivity C-reactive protein, oxidative stress markers such as oxidized low-density lipoprotein and diacron-reactive oxygen metabolites, and atherosclerosis indicators (cardio-ankle vascular index [CAVI] and ankle-brachial pressure index [ABI]) were measured.
Results: The median treatment duration was 28 months in the DNG group and 32.5 months in the OC group. Triglyceride levels were higher in the OC group than in the other three groups (P < 0.05). Regarding markers of inflammation and oxidative stress, log high-sensitivity C-reactive protein and diacron-reactive oxygen metabolites levels were higher in the untreated group than in the control group (P < 0.05), and these markers were further increased in the OC group (log high-sensitivity C-reactive protein: P < 0.05; diacron-reactive oxygen metabolites: P < 0.01), but not in the DNG group. There was no difference in the CAVI and ABI among all groups. Spearman correlation revealed a positive correlation between duration of OC therapy and CAVI (ρ = +0.49; P = 0.002), but no correlation between the duration of DNG therapy and CAVI (ρ = -0.04; P = 0.81). Conclusions: Inflammation and oxidative stress markers are increased in women with untreated endometriosis. Treatment with OC, but not with DNG, further increases these levels. There was a positive association between the duration of OC administration and atherosclerosis risk for women with endometriosis. Our results suggest that DNG could be administered to endometriosis without the increased atherosclerosis risk and short-term OC administration for endometriosis is not harmful, however, atherosclerosis risk should be strictly observed. PMID: 32715291 [PubMed]
https://www.globenewswire.com/news-release/2020/04/22/2020378/0/en/ObsEva-Announces-Publication-of-Abstracts-from-Phase-2b-EDELWEISS-Trial-of-Linzagolix-in-Endometriosis.html
ObsEva Announces Publication of Abstracts from Phase 2b EDELWEISS Trial of Linzagolix in Endometriosis
Myovant’s Endometriosis Treatment Hits the Mark in First of Two Phase III Trials
Myovant’s Endometriosis Treatment Hits the Mark in First of Two Phase III Trials
https://www.globenewswire.com/news-release/2020/04/22/2019886/0/en/Myovant-Sciences-Announces-Positive-Results-from-Phase-3-SPIRIT-2-Study-Evaluating-Once-Daily-Relugolix-Combination-Therapy-in-Women-with-Endometriosis-and-from-Ovulation-Inhibitio.html
Myovant Sciences Announces Positive Results from Phase 3 Study Evaluating Once-Daily Relugolix Combination Therapy in Women with Endometriosis and from Ovulation Inhibition Study
https://academic.oup.com/humrep/advance-article-abstract/doi/10.1093/humrep/deaa061/5821145?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/32303740?dopt=Abstract
Related Articles
Activation of ATF3/AP-1 signaling pathway is required for P2X3-induced endometriosis pain.
Hum Reprod. 2020 Apr 18;:
Authors: Ding S, Yu Q, Wang J, Zhu L, Li T, Guo X, Zhang X
Abstract
STUDY QUESTION: Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain?
SUMMARY ANSWER: Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system.
WHAT IS KNOWN ALREADY: Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain.
STUDY DESIGN, SIZE, DURATION: A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Degrees of hyperalgesia, endogenous adenosine 5′-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5′-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested.
MAIN RESULTS AND THE ROLE OF CHANCE: The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models.
LARGE SCALE DATA: N/A.
LIMITATIONS, REASONS FOR CAUTION: Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated.
WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor.
STUDY FUNDING/COMPETING INTEREST(S): This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests.
PMID: 32303740 [PubMed – as supplied by publisher]
https://www.mdpi.com/1422-0067/21/8/2840
https://www.ncbi.nlm.nih.gov/pubmed/32325785?dopt=Abstract
Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions.
Int J Mol Sci. 2020 Apr 18;21(8):
Authors: Luddi A, Marrocco C, Governini L, Semplici B, Pavone V, Luisi S, Petraglia F, Piomboni P
Abstract
Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.
PMID: 32325785 [PubMed – in process]
https://www.mdpi.com/1422-0067/21/8/2815
https://www.ncbi.nlm.nih.gov/pubmed/32316608?dopt=Abstract
Related Articles
Estrogen Receptors and Endometriosis.
Int J Mol Sci. 2020 Apr 17;21(8):
Authors: Chantalat E, Valera MC, Vaysse C, Noirrit E, Rusidze M, Weyl A, Vergriete K, Buscail E, Lluel P, Fontaine C, Arnal JF, Lenfant F
Abstract
Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERβ and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERβ in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.
PMID: 32316608 [PubMed – in process]
https://clinicaltrials.gov/ct2/show/NCT03213457?type=Intr&cond=Endometriosis&lupd_s=02%2F21%2F2019&lupd_d=14
Condition : Endometriosis
Interventions : Drug: Estradiol/Norethindrone Acetate; Other: Placebo for Elagolix; Drug: Elagolix; Other: Placebo for E2/NETA
Sponsor : AbbVie
Recruiting
A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain
NCT03213457
Tue, 11 Jul 2017 12:00:00 EDT
Last Update Posted: 03/07/19 12:39PM
https://clinicaltrials.gov/ct2/show/NCT04347135?type=Intr&cond=Endometriosis&lupd_s=04%2F01%2F2020&lupd_d=14
Condition : Endometriosis
Intervention : Drug: F-18 FES
Sponsor : Annie (Annie) T. Packard
Enrolling by invitation
Evaluating Endometriosis With 16α-(18)F-fluoro-17β-estradiol ([F-18] FES) PET/MRI
NCT04347135
Wed, 15 Apr 2020 12:00:00 EDT
Last Update Posted: 04/15/20 07:54AM
https://www.sciencedaily.com/releases/2020/04/200406190449.htm
https://www.iflscience.com/health-and-medicine/researchers-are-closing-in-on-a-treatment-for-endometriosis-using-nanotechnology/
Researchers use nanotechnology to develop new treatment for endometriosis
Date:
April 6, 2020
Source:
Oregon State University
Summary:
Scientists have developed a precise, nanotechnology-based treatment to alleviate the pain and fertility problems associated with endometriosis, a common gynecological condition in women of childbearing age.
https://rep.bioscientifica.com/view/journals/rep/aop/rep-19-0502/rep-19-0502.xml
https://www.ncbi.nlm.nih.gov/pubmed/32240980?dopt=Abstract
Clotrimazole reduces endometriosis and the estrogen concentration by downregulating aromatase.
Reproduction. 2020 Apr 01;:
Authors: Machado DE, Alessandra-Perini J, Menezes de Mendonça E, Claudino MC, Nasciutti LE, Sola-Penna M, Zancan P, Perini JA
Abstract
This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.
PMID: 32240980 [PubMed – as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pubmed/32242399?dopt=Abstract
Effect of herb-partitioned moxibustion on pain and quality of life in women with endometriosis: a protocol for a randomized clinical trial.
J Tradit Chin Med. 2020 Apr;40(2):324-332
Authors: Hu H, Chen L, Jin X, Li R, Fang J
Abstract
OBJECTIVE: To investigate the effect of herb-partitioned moxibustion (HPM) on pain and quality of life in women with endometriosis.
METHODS: Thirty-six patients will be randomly assigned to a treatment group or a wait-list control group. The treatment group will receive 12 sessions of HPM in the lower abdomen and lumbosacral region for 3 months. Wait-list participants will not receive any specific treatments until the trial is completed.
RESULTS: The primary outcome measure is pain intensity assessed by a Visual Analogue Scale at baseline, months 1, 2, and 3 in the treatment period, and months 4, 5, and 6 in the follow-up period. Secondary outcome measures include quality of life assessed by the Short Form 36 Health Survey, change in CA125, change in cyst diameter (assessed by ultrasound examination), and rescue medication dosage.
CONCLUSION: This study will provide evidence to confirm if HPM may be used as a therapeutic option for treating endometriosis.
PMID: 32242399 [PubMed – in process]
https://www.mdlinx.com/journal-summaries/endometriosis-diagnostics-testing-endometriosis/2020/03/17/7526191
Accurate diagnosis of endometriosis using serum microRNAs
https://www.tandfonline.com/doi/full/10.1080/03007995.2020.1744120
https://www.ncbi.nlm.nih.gov/pubmed/32175777?dopt=Abstract
Related Articles
Use of dienogest in endometriosis: a narrative literature review and expert commentary.
Curr Med Res Opin. 2020 Mar 16;:1
Authors: Murji A, Biberoğlu K, Leng J, Mueller MD, Römer T, Vignali M, Yarmolinskaya M
Abstract
Objective: Endometriosis affects up to 10% of women of reproductive age, and the main goal of treatment is to relieve symptoms. Progestins have been the mainstay of endometriosis suppression, of which dienogest has become an important option in many parts of the world. This is an expert literature review, with recommendations on the use of dienogest in the context of various clinical considerations when treating endometriosis.Methods: A search of PubMed was conducted for papers published between 2007-2019 on the use of dienogest in endometriosis. Experts reviewed these and included those they considered most relevant in clinical practice, according to their own clinical experience.Results: Evidence regarding the long-term use (> 15 months) of dienogest for the management of endometriosis is presented, with experts concluding that the efficacy of dienogest should be assessed primarily on its impact on pain and quality of life. Fertility preservation, the option to avoid or delay surgery, and managing bleeding irregularities that can occur with this treatment are also considered. Counseling women on potential bleeding risks before starting treatment may be helpful, and evidence suggests that few women discontinue treatment for this reason, with the benefits of treatment outweighing any impact of bleeding irregularities.Conclusions: Overall, the evidence demonstrates that dienogest offers an effective and tolerable alternative or adjunct to surgery and provides many advantages over combined hormonal contraceptives for the treatment of endometriosis. It is important that treatment guidelines are followed and care is tailored to the woman’s individual needs and desires.
PMID: 32175777 [PubMed – as supplied by publisher]
https://www.ajog.org/article/S0002-9378(20)30321-5/pdf
https://www.ncbi.nlm.nih.gov/pubmed/32165186?dopt=Abstract
Related Articles
Accurate Diagnosis of Endometriosis Using Serum MicroRNAs.
Am J Obstet Gynecol. 2020 Mar 09;:
Authors: Moustafa S, Burn M, Mamillapalli R, Nematian S, Flores V, Taylor HS
Abstract
BACKGROUND: Endometriosis, a chronic disease that afflicts millions of women worldwide, has traditionally been diagnosed by laparoscopic surgery. This diagnostic barrier delays identification and treatment by years, resulting in prolonged pain and disease progression. Development of a non-invasive diagnostic test could significantly improve timely disease detection. We tested the feasibility of serum microRNAs as diagnostic biomarkers of endometriosis in women with gynecologic disease symptoms.
OBJECTIVE: To validate the use of a microRNA panel as a non-invasive diagnostic method for detecting endometriosis.
STUDY DESIGN: This was a prospective study evaluating subjects with a clinical indication for gynecologic surgery in an academic medical center. Serum samples were collected prior to surgery from 100 subjects. Women were selected based on the presence of symptoms and laparoscopy was performed to determine the presence or absence of endometriosis. The control group was categorized based on absence of visual disease at the time of surgery. Circulating miRNAs miR-125b-5p, miR-150-5p, miR-342-3p, miR-451a, miR-3613-5p and let-7b were measured in serum by qRT-PCR in a blinded fashion, without knowledge of disease status. Receiver operating characteristic (ROC) analysis was performed on individual miRNAs, as well as combinations of miRNAs. An algorithm combining the expression values of these miRNAs, built using machine learning with a Random Forest classifier, was generated to predict the presence or absence of endometriosis on operative findings. This algorithm was then tested in an independent dataset of 48 previously identified subjects not included in the training set (24 endometriosis and 24 controls) to validate its diagnostic performance.
RESULTS: The mean age of women in the study population was 34.1 and 36.9 for the endometriosis and control groups, respectively. Control group subjects displayed varying pathologies, with leiomyoma occurring the most often (n=39). Subjects with endometriosis had significantly higher expression levels of four serum miRNAs: miR-125b-5p, miR-150-5p, miR-342-3p, and miR-451a. Two serum miRNAs showed significantly lower levels in the endometriosis group: miR-3613-5p and let-7b. Individual miRNAs had ROC areas under the curve (AUC) ranging from 0.68 to 0.92. A classifier combining these miRNAs yielded an AUC of 0.94 when validated in the independent set of subjects not included in the training set. Analysis of the expression levels of each miRNA based on rASRM staging revealed that all miRNAs could distinguish Stage I/II from control, and Stage III/IV from control, but that the difference between Stage I/II and Stage III/IV was not significant. Subgroup analysis revealed that neither phase of menstrual cycle or use of hormonal medication significantly impacted expression levels in the miRNAs used in our algorithm.
CONCLUSIONS: This is the first report showing that miRNA biomarkers can reliably differentiate between endometriosis and other gynecologic pathologies with an AUC > 0.9 across two independent studies. We validated the performance of an algorithm based on previously identified miRNA biomarkers, demonstrating their potential to detect endometriosis in a clinical setting, allowing earlier identification and treatment. The ability to diagnose endometriosis non-invasively could reduce the time to diagnosis, surgical risk, years of discomfort, disease progression, associated co-morbidities and healthcare costs.
PMID: 32165186 [PubMed – as supplied by publisher]
https://www.abc.net.au/news/2020-03-06/the-long-road-to-diagnose-endometriosis-not-just-menstruation/12017718
Endometriosis diagnosis taking years as women given outdated advice when seeking treatment
https://www.bbc.com/news/uk-england-beds-bucks-herts-51708887
Women with endometriosis ‘finally being believed’
https://clinicaltrials.gov/ct2/show/NCT04173169?type=Intr&cond=Endometriosis&lupd_s=11%2F07%2F2019&lupd_d=14
Conditions : Infertility; Endometriosis
Interventions : Drug: Elagolix 200 MG; Drug: Placebo
Sponsors : Yale University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Colorado, Denver; Northwestern University; University of North Carolina
Not yet recruiting
Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis – A Prospective Double-blind Placebo-controlled Trial
NCT04173169
Thu, 21 Nov 2019 12:00:00 EST
Last Update Posted: 11/21/19 07:46AM
https://pubmed.ncbi.nlm.nih.gov/32107990-a-review-of-aberrant-dna-methylation-and-epigenetic-agents-targeting-dna-methyltransferase-in-endometriosis/
https://www.ncbi.nlm.nih.gov/pubmed/32107990?dopt=Abstract
http://www.eurekaselect.com/179821/article
A review of aberrant DNA methylation and epigenetic agents targeting DNA methyltransferase in endometriosis.
Curr Drug Targets. 2020 Feb 27;:
Authors: Yang L, Ding L, Ren C, Zhang H, Lu J, Wang S, Wu Z, Yang Y
Abstract
BACKGROUND: Endometriosis (EMs)is a gynecological disease defined by the endometrial tissue appearing in other tissues or organs outside the uterus. Its clinical manifestations are dysmenorrhea, irregular menstruation, even infertility. Although EMs is a benign disease, it has the characteristics of malignant tumor and has the potential of malignant transformation. Recent studies have found that endometriosis may involve epigenetic changes and various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Among them, aberrant DNA methylation is the main form. Previous studies have elucidated the epigenetic components of endometriosis and reported variations in epigenetic patterns of genes known to be associated with abnormal hormonal, immune, and inflammatory states of endometriosis. With the development of high-throughput sequencing and other biomolecular technologies，we have a better understanding of genome-wide methylation in endometriosis.
OBJECTIVE: But the epigenetic drugs targeting of DNA methylation in the therapy of endometriosis hasn’t been elaborated systematically.
RESULTS: This article review the role of DNA methylation in the pathophysiology of endometriosis and provide the insight into the mechanisms underlining the potential application of targeting of DNA methylation modifiers as a novel therapeutic approach for endometriosis. We also review current progress in using DNA methylation inhibitors in EMs therapy and the potential promise and challenges ahead.
CONCLUSION: Aberrant DNA methylation plays an essential role in the pathogenesis of endometriosis and epigenetic agents targeting DNA methyltransferase is expected to be the theoretical basis for the new treatment of endometriosis.
PMID: 32107990 [PubMed – as supplied by publisher]
https://graziadaily.co.uk/life/in-the-news/endometriosis-inquiry/
https://endometriosis-uk.org/news/mps-launch-inquiry-investigate-challenges-faced-15-million-endometriosis-37618#.XltMtRNKg4c
MPs Have Launched An Enquiry Into Endometriosis To Improve Diagnosis, Treatment And Support
And you can take part by filing in the survey…
https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-020-0381-0
https://www.ncbi.nlm.nih.gov/pubmed/32082539?dopt=Abstract
https://pubmed.ncbi.nlm.nih.gov/32082539-apoptotic-functions-of-micrornas-in-pathogenesis-diagnosis-and-treatment-of-endometriosis/?dopt=Abstract
Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis.
Cell Biosci. 2020;10:12
Authors: Taghavipour M, Sadoughi F, Mirzaei H, Yousefi B, Moazzami B, Chaichian S, Mansournia MA, Asemi Z
Abstract
MicroRNAs or miRNAs are a component of the non-coding RNAs family which is engaged in many cellular functions such as cell proliferation, apoptosis, gene expression, signaling pathways, angiogenesis, and etc. Endometriosis is a malignant gynecologic disorder occurring in women before menopausal age. Pathogenesis of this illness is still a discussion subject between the scientists but in our knowledge, microRNAs can be one of the possible involved factors. The purpose of this paper is to investigate the role of apoptotic activities of miRNAs in endometriosis. Accumulative evidence has demonstrated the role of cell proliferation, apoptosis, and invasion in the progression of these diseases. In this review, we looked into the specific role of apoptosis and its related genes and pathways in endometriosis and tied to present an explanation of how miRNAs can affect endometriosis by their apoptotic activities. What we found is that a great extent of miRNAs is involved in this illness and they are responsible for repressing apoptosis and progression of the disease. As a result, miRNAs have two different usages in endometriosis: biomarkers and potential therapeutic targets. In this review we gathered a great amount of evidence to inquire into the role of micro RNAs in inducing apoptosis and how this mechanism can be exerted for therapeutic purposes for endometriosis.
PMID: 32082539 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT03709420?type=Intr&cond=Endometriosis&lupd_s=07%2F26%2F2019&lupd_d=14
Condition : Endometriosis
Interventions : Drug: Placebo; Drug: FOR-6219
Sponsors : Forendo Pharma Ltd; Richmond Pharmacology Limited
Recruiting
A Study to Investigate the Safety, Tolerability, Food Effect, Pharmacokinetics and Pharmacodynamics of FOR-6219
NCT03709420
Wed, 17 Oct 2018 12:00:00 EDT
Last Update Posted: 08/09/19 07:12AM
https://www.labiotech.eu/medical/searching-endometriosis-treatment/
https://www.labiotech.eu/wp-content/uploads/2020/02/1_In-Search-for-an-Endometriosis-Treatment_Evotec_Labiotech_2020.jpg
https://www.evotec.com/en/invest/news–announcements/press-releases/p/excelling-together-for-the-benefit-of-women-suffering-from-endometriosis-5671
Infographic: How Can We Find an Effective Endometriosis Treatment?
https://www.fertstert.org/article/S0015-0282(19)32457-4/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/32106991?dopt=Abstract
Related Articles
Interventions for endometriosis-related infertility: a systematic review and network meta-analysis.
Fertil Steril. 2020 02;113(2):374-382.e2
Authors: Hodgson RM, Lee HL, Wang R, Mol BW, Johnson N
Abstract
OBJECTIVE: To compare the effectiveness of different treatments for women with endometriosis-related infertility.
DESIGN: A systematic review and network meta-analysis of randomized controlled trials (RCTs).
SETTING: Not applicable.
PATIENT(S): Women with endometriosis confirmed by laparoscopy with associated infertility.
INTERVENTION(S): An extensive electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, ClinicalTrials.gov, and Embase.
MAIN OUTCOME MEASURE(S): Clinical pregnancy, live birth rate, miscarriage, and adverse events.
RESULT(S): A total of 4,252 trials/abstracts were identified through the literature search, of which we included 36 trials in the systematic review and 26 trials reporting on 2,245 women with endometriosis-related infertility in the network meta-analysis. Network meta-analysis showed that compared with placebo, surgical laparoscopy alone (odds ratio = 1.63; 95% confidence interval, 1.13-2.35) or GnRH agonist alone (odds ratio = 1.68; 95% confidence interval, 1.07-2.46) results in higher odds of pregnancy. The evidence on the other interventions versus placebo or on the secondary outcomes including live birth, miscarriage, and adverse events is insufficient.
CONCLUSION(S): The most important conclusion is that more RCTs are needed to clarify the relative effectiveness of treatments for endometriosis-related infertility, ideally comparing interventions to existing recommended interventions such as surgical laparoscopy. In addition, further RCTs comparing IVF and IUI to other treatments are essential.
REGISTRATION NUMBER: PROSPERO registration number, CRD42018087572.
PMID: 32106991 [PubMed – indexed for MEDLINE]
https://clinicaltrials.gov/ct2/show/NCT03840993
https://medicalxpress.com/news/2020-01-cannabinoids-symptoms-mice-endometriosis.html
Cannabinoids improve symptoms in mice with endometriosis
https://www.upf.edu/web/e-noticies/arxiu/-/asset_publisher/wEpPxsVRD6Vt/content/id/231450432/
Cannabinoids improve symptoms in mice with endometriosis
A new study suggests that cannabinoids can alleviate some symptoms of endomietrosis, the findings pave the way for further clinical research.
Tiny Fibers Carrying Curcumin May Be Targeted Endometriosis Treatment, Study Suggests
Tiny Fibers Carrying Curcumin May Be Targeted Endometriosis Treatment, Study Suggests
https://www.jpagonline.org/article/S1083-3188(19)30365-1/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/31812704?dopt=Abstract
Related Articles
Adolescent Endometriosis: An Update.
J Pediatr Adolesc Gynecol. 2020 Apr;33(2):112-119
Authors: Shim JY, Laufer MR
Abstract
Endometriosis is the leading pathologic cause of dysmenorrhea and chronic pelvic pain among adolescents. The appearance of endometriosis in adolescents may be different from that in female adults, resulting in delayed recognition and intervention. This article addresses the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of endometriosis in the adolescent.
PMID: 31812704 [PubMed – indexed for MEDLINE]
https://www.nhs.uk/news/cancer/early-research-points-possible-new-endometriosis-treatment/
Early research points to possible new endometriosis treatment
https://medicalxpress.com/news/2019-12-endometriosis-cancer-drug.html
Endometriosis could be treated with cancer drug, study suggests
https://www.sciencealert.com/the-most-common-disease-you-ve-never-heard-of-is-being-handled-with-dangerous-drugs
The ‘Most Common Disease You’ve Never Heard Of’ Is Being Handled With Dangerous Drugs
CARLY CASSELLA
19 NOV 2019
Too many patients with endometriosis are being prescribed opioids and not enough people are aware. Not even physicians.
https://medicalxpress.com/news/2019-11-australian-women-cannabis-endometriosis-symptoms.html
Australian women turning to cannabis to treat endometriosis symptoms
https://www.sciencealert.com/research-has-ignored-endometriosis-for-decades-and-it-s-now-costing-all-of-us
Research Has Ignored Endometriosis For Decades, And It’s Now Costing All of Us
https://www.tandfonline.com/doi/abs/10.1080/09513590.2019.1675045?journalCode=igye20
https://www.ncbi.nlm.nih.gov/pubmed/31607185?dopt=Abstract
Related Articles
Endometriosis – a decade later – still an enigmatic disease. What is the new in the diagnosis and treatment?
Gynecol Endocrinol. 2019 Oct 12;:1-5
Authors: Marian S, Hermanowicz-Szamatowicz K
Abstract
Endometriosis is a common disease in women of reproduction age. It causes pain and difficulty in getting pregnant. However the exact causes of infertility associated with endometriosis still remain controversial. The treatment of endometriosis consists of medical treatment of pain as well as medical and surgical treatment of infertility caused by endometriosis and assisted reproduction techniques. Since the treatment of endometriosis is often connected with diminishing ovarian reserve, the techniques for ovarian tissue preservation and oocyte and embryo freezing are used to maintain the ability for childbearing.
PMID: 31607185 [PubMed – as supplied by publisher]
https://www.sciencedirect.com/science/article/abs/pii/S2468784719301965?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/31563698?dopt=Abstract
Ginsenoside Rg3 attenuates endometriosis by inhibiting the viability of human ectopic endometrial stromal cells through the nuclear factor-kappaB signaling pathway.
J Gynecol Obstet Hum Reprod. 2019 Sep 26;:101642
Authors: Huang R, Chen S, Zhao M, Li Z, Zhu L
Abstract
OBJECTIVE: To investigate the effects of ginsenoside Rg3 on human ectopic endometriotic stromal cells in vitro.
MATERIALS AND METHODS: Ectopic endometrial tissue specimens were obtained from 6 female patients with ovarian endometriosis who underwent laparoscopic surgical procedures. Endometrial stromal cells derived from isolated ectopic endometriotic lesions were cultured, and the purity and homogeneity of cells were verified by Immunocytochemistry. The effect of Rg3 on cell proliferation was detected by Cell Counting Kit-8 (CCK8). After treatment with Rg3, the protein expression of NF-κB p65 subunit, VEGF, and caspases3 were measured by western blot analysis. Meanwhile, the mRNA expression of NF-κB p65 subunit was determined by Quantitative real-time polymerase chain reaction (RT-PCR).
RESULTS: Rg3 inhibited the proliferation of ectopic endometriotic cells in a time- and dose-dependent manner. The treatment with Rg3 significantly diminished the level of NF-κB p65 subunit as well as TNF-α induced nuclear translocation of NF-κB p65 subunit in ectopic endometriotic cells. Moreover, Rg3 upregulated the expression of caspases3 but suppressed the expression of VEGF.
CONCLUSION: Our results indicate that Ginsenoside Rg3 suppresses endometriosis by reducing the viability of human ectopic endometrial stromal cells involving the nuclear factor-kappaB signaling pathway in vitro.
PMID: 31563698 [PubMed – as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757391/
https://www.ncbi.nlm.nih.gov/pubmed/31547870?dopt=Abstract
Related Articles
miR-205-5p inhibits human endometriosis progression by targeting ANGPT2 in endometrial stromal cells.
Stem Cell Res Ther. 2019 Sep 23;10(1):287
Authors: Zhou CF, Liu MJ, Wang W, Wu S, Huang YX, Chen GB, Liu LM, Peng DX, Wang XF, Cai XZ, Li XX, Feng WQ, Ma Y
Abstract
BACKGROUND: miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular mechanisms remain unknown.
METHODS: miRNA microarray analysis was used to determine the expression profiling of EC fresh tissues. qRT-PCR was performed to screen miR-205-5p expression in EC tissues. The roles of miR-205-5p and its candidate target gene, angiopoietin-2 (ANGPT2), in endometriosis progression were confirmed on the basis of both in vitro and in vivo systems. miR-205-5p and ANGPT2 expression were measured by in situ hybridization and immunochemistry, and their clinical significance was statistically analysed.
RESULTS: miR-205-5p was screened as a novel suppressor of endometriosis through primary ectopic endometrial stromal cell migration, invasion, and apoptosis assay in vitro, along with endometrial-like xenograft growth and apoptosis in vivo. In addition, ANGPT2 was identified as a direct target of miR-205-5p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of ANGPT2 could respectively rescue and simulate the effects induced by miR-205-5p. Importantly, the miR-205-5p-ANGPT2 axis was found to activate the ERK/AKT pathway in endometriosis. Finally, miR-205-5p and ANGPT2 expression were closely correlated with the endometriosis severity.
CONCLUSION: The newly identified miR-205-5p-ANGPT2-AKT/ERK axis illustrates the molecular mechanism of endometriosis progression and may represent a novel diagnostic biomarker and therapeutic target for disease treatment.
PMID: 31547870 [PubMed – in process]
https://insight.jci.org/articles/view/128846
https://www.ncbi.nlm.nih.gov/pubmed/31534048?dopt=Abstract
Related Articles
Extracellular vesicles from endometriosis patients are characterized by a unique miRNA-lncRNA signature.
JCI Insight. 2019 Sep 19;4(18):
Authors: Khalaj K, Miller JE, Lingegowda H, Fazleabas AT, Young SL, Lessey BA, Koti M, Tayade C
Abstract
With multifactorial etiologies, combined with disease heterogeneity and a lack of suitable diagnostic markers and therapy, endometriosis remains a major reproductive health challenge. Extracellular vesicles (EVs) have emerged as major contributors of disease progression in several conditions, including a variety of cancers; however, their role in endometriosis pathophysiology has remained elusive. Using next-generation sequencing of EVs obtained from endometriosis patient tissues and plasma samples compared with controls, we have documented that patient EVs carry unique signatures of miRNAs and long noncoding RNAs (lncRNAs) reflecting their contribution to disease pathophysiology. Mass spectrophotometry-based proteomic analysis of EVs from patient plasma and peritoneal fluid further revealed enrichment of specific pathways, as well as altered immune and metabolic processes. Functional studies in endometriotic epithelial and endothelial cell lines using EVs from patient plasma and controls clearly indicate autocrine uptake and paracrine cell proliferative roles, suggestive of their involvement in endometriosis. Multiplex cytokine analysis of cell supernatants in response to patient and control plasma-derived EVs indicate robust signatures of important inflammatory and angiogenic cytokines known to be involved in disease progression. Collectively, these findings suggest that endometriosis-associated EVs carry unique cargo and contribute to disease pathophysiology by influencing inflammation, angiogenesis, and proliferation within the endometriotic lesion microenvironment.
PMID: 31534048 [PubMed – in process]
https://www.karger.com/Article/Abstract/502258
https://www.ncbi.nlm.nih.gov/pubmed/31527378?dopt=Abstract
Related Articles
Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival.
Gynecol Obstet Invest. 2019 Sep 17;:1-10
Authors: Li J, Zeng Z, Chang Y, Li M, Wu Q, Chen P, Liang X
Abstract
BACKGROUND/AIMS: The identification of new compound candidates for endometriosis treatment is needed. Cyclooxygenase-2 (COX-2) is considered a crucial target to control the progress and recurrence of endometriosis. Here, we identified ursolic acid (UA) as a natural inhibitor of COX-2 and investigated its effects on endometriosis progression.
METHODS: Primary human endometriotic stromal cells isolated from patients with endometriosis were exposed to UA at concentrations of 15, 30, 45, and 60 μM. 3-(4,5-Dimethylthiaziazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, 5′-bromo-2′-deoxy-uridine assays, and Caspase-3 activity measurements were performed to detect cell growth and apoptosis. Enzyme-linked immunosorbent assays were used to detect COX-2 and vascular endothelial growth factor (VEGF) protein expression and prostaglandin E2 (PGE2) levels. Capillary-tubule formation assays using human umbilical vein endothelial cells were also carried out to determine angiogenesis.
RESULTS: UA significantly decreased cell viability, inhibited proliferation, and increased caspase-3 activity in a dose-dependent manner. COX-2 protein expression and the subsequent PGE2 production were both reduced by UA. Meanwhile, UA exposure decreased VEGF secretion in the stromal cells and the capillary-tubule formation assay confirmed the inhibitory effect of UA on angiogenesis. Furthermore, UA increased the phosphorylation of c-Jun N-terminal kinase and p38.
CONCLUSIONS: Our data suggest that UA plays a role as a natural inhibitor of COX-2 to control the survival of human endometriotic stromal cells by inhibiting proliferation and angiogenesis and promoting apoptosis.
PMID: 31527378 [PubMed – as supplied by publisher]
https://onlinelibrary.wiley.com/doi/abs/10.1111/aji.13182
https://www.ncbi.nlm.nih.gov/pubmed/31446641?dopt=Abstract
Tokishakuyakusan, a Kampo medicine, attenuates endometriosis like lesions and hyperalgesia in murine with endometriosis like symptoms
Am J Reprod Immunol. 2019 Aug 24;:e13182
Authors: Nagira K, Taniguchi F, Nakamura K, Tokita Y, Tsuchiya N, Yin Mon K, Harada T
Abstract
PROBLEM: How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model?.
METHODS: BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice, and collected blood samples before sacrifice. Then the endometriosis-like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio-Plex Suspension Array System. IL-33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis-like lesions or the eutopic endometrium were evaluated by real time RT-PCR.
RESULTS: After 14 days TSS treatment, the numbers of endometriosis like cysts and cyst weight were significantly decreased. In TSS treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL-33 mRNA expression in endometriosis like lesions and led to the tendency of attenuation of the elevated IL-33 synthesis in the cyst fluids of lesions.
CONCLUSION: These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS-accelerated endometriosis like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea. This article is protected by copyright. All rights reserved.
PMID: 31446641 [PubMed – as supplied by publisher]
https://www.biospace.com/article/forendo-pharma-commences-phase-1b-proof-of-mechanism-study-with-its-lead-endometriosis-program-hsd17b1-inhibitor-for-6219/
Forendo Pharma commences Phase 1b Proof of Mechanism study with its lead endometriosis program, HSD17B1 inhibitor FOR-6219
http://ijms.sums.ac.ir/article_44970.html
https://www.ncbi.nlm.nih.gov/pubmed/31439975?dopt=Abstract
Related Articles
Combination Effect of Caffeine and Caffeic Acid Treatment on the Oxidant Status of Ectopic Endometrial Cells Separated from Patients with Endometriosis.
Iran J Med Sci. 2019 Jul;44(4):315-324
Authors: Jamali N, Mostafavi-Pour Z, Zal F, Kasraeian M, Poordast T, Ramezani F, Zare R
Abstract
Background: Endometriosis is a common gynecological disease in which oxidative stress is a potential factor. Caffeine and caffeic acid are present in various foods and beverages with anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. In this study, we aimed to investigate the ameliorative effects of caffeine, caffeic acid, and caffeine+caffeic acid treatments on oxidative stress in ectopic endometrial cells taken from patients and eutopic ones from women without endometriosis.
Methods: In this experimental study, eutopic and ectopic endometrial cells were obtained from biopsies of women free of disease (n=10) and patients with endometriosis (n=10) who referred to Shiraz reference hospitals (2017-2018). Both eutopic and ectopic endometrial cells were divided into four groups: Treated with caffeine, with caffeic acid, with caffeine+caffeic acid, and the control. Also, antioxidant enzyme activities and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined in each group. The data were analyzed using independent sample t test and one-way ANOVA followed by Tukey post-hoc test.
Results: Caffeic acid, but not caffeine treatment demonstrated a decrease in MDA level (P<0.001) as well as an increase in GSH level (P<0.001) and antioxidant enzyme activities in ectopic endometrial cells. Also, the treatment of the cells with caffeine+caffeic acid caused similar effects as those ectopic cells treated with caffeic acid. Conclusion: According to the findings of the present study, caffeic acid reduced oxidative stress which may alleviate the complications associated with endometriosis. However, more investigations are needed for evaluating the efficiency and safety of caffeic acid. PMID: 31439975 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT02832271?type=Intr&cond=Endometriosis&lupd_s=07%2F11%2F2019&lupd_d=14
Condition : Endometriosis
Interventions : Drug: SUNPHENON EGCg; Drug: Placebo
Sponsors : Chinese University of Hong Kong; University of Chinese Academy of Sciences; Sun Yat-sen University; Guangdong Provincial Hospital of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine
Recruiting
Green Tea for Endometriosis
NCT02832271
Thu, 14 Jul 2016 12:00:00 EDT
Last Update Posted: 07/25/19 07:34AM
https://www.clinicsjournal.com/article/nanotechnology-for-the-treatment-of-deep-endometriosis-uptake-of-lipid-core-nanoparticles-by-ldl-receptors-in-endometriotic-foci/
Nanotechnology for the treatment of deep endometriosis: a promising therapeutic option
http://ijfs.ir/journal/article/abstract/5584
https://www.ncbi.nlm.nih.gov/pubmed/31310070?dopt=Abstract
Beneficial Effects of Oral Lactobacillus on Pain Severity in Women Suffering from Endometriosis: A Pilot Placebo-Controlled Randomized Clinical Trial.
Int J Fertil Steril. 2019 Oct;13(3):178-183
Authors: Khodaverdi S, Mohammadbeigi R, Khaledi M, Mesdaghinia L, Sharifzadeh F, Nasiripour S, Gorginzadeh M
Abstract
Background: This study assessed the effects of a lactobacillus-based medication on pain intensity scores in women with endometriosis.
Materials and Methods: The present randomized pilot placebo-controlled trial was done on eligible women who were surgically and pathologically diagnosed with endometriosis. Thirty-seven participants who had not received hormonal treatment in the last three months, were enrolled and randomized into LactoFem® and placebo groups. Lactobacillus capsules or placebo were administrated orally once a day for 8 weeks. Patients were assessed for pain severity using Visual Analogue Scale (VAS) scores for dysmenorrhea, dyspareunia and chronic pelvic pain at baseline and after 8 and 12 weeks post-intervention.
Results: Mean age of participants and mean body mass index (BMI) for the LactoFem® and control groups were comparable. All patients had stage 3 and 4 of the disease based on revised American fertility society (AFS) classification of endometriosis. Mean initial pain scores for dysmenorrhea, dyspareunia and chronic pelvic pain were 6.53 ± 2.88, 4.82 ± 3.76 and 4.19 ± 3.53, respectively in the LactoFem® group and 5.60 ± 2.06, 3.67 ± 2.64 and 2.88 ± 2.80, respectively for the control group; the two groups had comparable scores in this regard. There was more decrease in pain scores for both dysmenorrhea and the overall pain after 8 weeks of treatment in LactoFem® group compared to the control group. The scores for dysmenorrhea were 6.53 ± 2.88 and 5.60 ± 2.06 in the LactoFem® and control groups, respectively, before intervention but, after 8-week treatment, these values were 3.07 ± 2.49 and 4.47 ± 2.13 (P=0.018), respectively. The changes in overall pain score in the LactoFem® and control group during this period were 7.33 ± 7.00 and 4.11 ± 1.68, respectively (P=0.017).
Conclusion: This study showed some beneficial effects of lactobacillus administration on endometriosis-related pain (Registration number: IRCT20150819023684N5).
PMID: 31310070 [PubMed]
Macrophages identified as cause of endometriotic pain
Researchers have discovered that macrophages are a key cause for pain in women with endometriosis so could be a treatment target for the condition.
https://medicalxpress.com/news/2019-07-endometriosis-immune-cell-discovery-relief.html
Endometriosis: Immune cell discovery could provide relief for women with ‘hidden’ painful disorder
https://www.nih.gov/news-events/news-releases/nih-scientists-identify-spasm-women-endometriosis-associated-chronic-pelvic-pain
NIH scientists identify spasm in women with endometriosis-associated chronic pelvic pain
https://www.epmmagazine.com/news/scientists-discover-key-cause-of-pain-for-women-with/
Scientists discover key cause of pain for women with endometriosis – potentially leading the way for new kinds of pain relief for the condition
Scientists have discovered a key cause for pelvic pain experienced by women with endometriosis, potentially leading the way for new kinds of pain relief for the condition.
https://www.fasebj.org/doi/10.1096/fj.201900797R
https://www.ncbi.nlm.nih.gov/pubmed/31291762?dopt=Abstract
Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis.
FASEB J. 2019 Jul 10;:fj201900797R
Authors: Forster R, Sarginson A, Velichkova A, Hogg C, Dorning A, Horne AW, Saunders PTK, Greaves E
Abstract
Endometriosis is a common incurable inflammatory disorder that is associated with debilitating pelvic pain in women. Macrophages are central to the pathophysiology of endometriosis: they dictate the growth and vascularization of endometriosis lesions and more recently have been shown to promote lesion innervation. The aim of this study was to determine the mechanistic role of macrophages in producing pain associated with endometriosis. Herein, we show that macrophage depletion in a mouse model of endometriosis can reverse abnormal changes in pain behavior. We identified that disease-modified macrophages exhibit increased expression of IGF-1 in an in vitro model of endometriosis-associated macrophages and confirmed expression by lesion-resident macrophages in mice and women. Concentrations of IGF-1 were elevated in peritoneal fluid from women with endometriosis and positively correlate with their pain scores. Mechanistically, we demonstrate that macrophage-derived IGF-1 promotes sprouting neurogenesis and nerve sensitization in vitro. Finally, we show that the Igf-1 receptor inhibitor linsitinib reverses the pain behavior observed in mice with endometriosis. Our data support a role for macrophage-derived IGF-1 as a key neurotrophic and sensitizing factor in endometriosis, and we propose that therapies that modify macrophage phenotype may be attractive therapeutic options for the treatment of women with endometriosis-associated pain.-Forster, R., Sarginson, A., Velichkova, A., Hogg, C., Dorning, A., Horne, A. W., Saunders, P. T. K., Greaves, E. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis.
PMID: 31291762 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04012034?type=Intr&cond=Endometriosis&lupd_s=06%2F25%2F2019&lupd_d=14
Conditions : Endometriosis; Chronic Pain; Quality of Life
Interventions : Device: Radiofrequency A; Device: Radiofrequency B
Sponsor : Hospital Clinic of Barcelona
Recruiting
Treatment With Radiofrequency in Patients With Chronic Pelvic Pain and History of Endometriosis
NCT04012034
Tue, 09 Jul 2019 12:00:00 EDT
Last Update Posted: 07/09/19 07:35AM
https://www.ncbi.nlm.nih.gov/pubmed/31274059?dopt=Abstract
Dose-Dependent Decreased Fertility in Response to the Burden of Endometriosis in a Murine Model.
Reprod Sci. 2019 Jul 05;:1933719119859438
Authors: Rosa-E-Silva ACJS, Rosa-E-Silva JC, Mamillapalli R, Taylor HS
Abstract
Endometriosis is a gynecological disease caused by the growth of endometrial cells outside the uterus leading to inflammation, pelvic pain, and infertility. The relationship between the amount of ectopic uterine tissue growth and the severity of symptoms is still unclear. The presence or degree of pain and infertility does not correlate with the stage of disease as currently defined. Here, we report a clear dose-response relationship between the amount of ectopic tissue transplanted and the reproductive outcomes in a murine model of endometriosis. Endometriosis was induced in mice using various amounts of transplanted uterine tissue. Four groups of mice consisted of a sham surgery control or those transplanted with 1, 2, or 4 endometrial segments of 5 mm each. Pregnancy rates were significantly lower in those transplanted with 2 or 4 segments compared to sham or the 1 segment groups. We demonstrate that infertility does correlate with the extent of active disease. Current clinical staging systems do not account for disease activity and may inappropriately weight sequela of disease. Early recognition and treatment in women may help to minimize the effect of endometriosis on fertility. Here, we describe a mouse model of endometriosis and infertility that may be useful to elucidate the mechanisms of infertility in endometriosis.
PMID: 31274059 [PubMed – as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pubmed/31299634?dopt=Abstract
Elevated heme impairs macrophage phagocytosis in endometriosis.
Reproduction. 2019 Jul 01;:
Authors: Liu YY, Liu YK, Hu WT, Tang LL, Sheng YR, Wei CY, Li MQ, Zhu XY
Abstract
Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22μmol/L, 95% confidence interval [CI]:12.54 to 16.71), compared with the EMS-free group (9.517μmol/L, 95%CI: 8.891 to 10.1053). This abnormal accumulation was not associated with the color of PF, the phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophage (pMφs) was observed in the EMS group. Consistently, a high concentration (30μmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low concentration (10μmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) and the CD14+ peripheral monocytes (CD14+ Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pMφs in EMS.
PMID: 31299634 [PubMed – as supplied by publisher]
https://academic.oup.com/humrep/article-abstract/34/7/1225/5523893?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/31247078?dopt=Abstract
Related Articles
B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice.
Hum Reprod. 2019 07 08;34(7):1225-1234
Authors: Riccio LGC, Jeljeli M, Santulli P, Chouzenoux S, Doridot L, Nicco C, Reis FM, Abrão MS, Chapron C, Batteux F
Abstract
STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis?
SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton’s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect.
WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear.
STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation.
PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA.
MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice.
LARGE SCALE DATA: N/A.
LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans.
WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis.
STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.
PMID: 31247078 [PubMed – indexed for MEDLINE]
https://www.jmig.org/article/S1553-4650(19)30290-0/fulltext
High-Intensity Focused Ultrasound in the Treatment of Abdominal Wall Endometriosis
https://clinicaltrials.gov/ct2/show/NCT03994432?type=Intr&cond=endometriosis&rank=8
Effect of Mediterranean Diet and Physical Activity in Patients With Endometriosis (PHAMEDENDO)
https://clinicaltrials.gov/ct2/show/NCT02778399?type=Intr&cond=Endometriosis&lupd_s=05%2F27%2F2019&lupd_d=14
Condition : Endometriosis
Interventions : Drug: Placebo; Drug: OBE2109
Sponsor : ObsEva SA
Active, not recruiting
A Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis
NCT02778399
Thu, 19 May 2016 12:00:00 EDT
Last Update Posted: 06/10/19 10:02AM
https://clinicaltrials.gov/ct2/show/NCT03978013?type=Intr&cond=Endometriosis&lupd_s=05%2F23%2F2019&lupd_d=14
Conditions : PCOS; Endometriosis; Advised Maternal Age; Male Factor Infertility
Interventions : Other: Pomegranate juice; Other: Apple juice
Sponsor : Rambam Health Care Campus
Not yet recruiting
Pomegranate Juice Effect on Oxidative Stress in Infertile Women During IVF Treatment
NCT03978013
Thu, 06 Jun 2019 12:00:00 EDT
Last Update Posted: 06/06/19 07:30AM
https://clinicaltrials.gov/ct2/show/NCT02778919?type=Intr&cond=Endometriosis&lupd_s=05%2F21%2F2019&lupd_d=14
Condition : Endometriosis
Interventions : Drug: KLH-2109; Drug: Placebo; Drug: Leuprorelin acetate
Sponsor : Kissei Pharmaceutical Co., Ltd.
Completed
Late Phase II Clinical Study of KLH-2109 in Patients With Endometriosis
NCT02778919
Fri, 20 May 2016 12:00:00 EDT
Last Update Posted: 06/04/19 07:01AM
https://link.springer.com/article/10.1007%2Fs00424-019-02283-2
https://www.ncbi.nlm.nih.gov/pubmed/31129698?dopt=Abstract
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miR-141-3p affects apoptosis and migration of endometrial stromal cells by targeting KLF-12.
Pflugers Arch. 2019 May 25;:
Authors: Zhang Y, Yan J, Pan X
Abstract
Endometriosis is an estrogen-dependent disease that is characterized by pelvic pain and infertility. MicroRNAs have been shown to implicate in the progression of endometriosis. In our study, we used real-time PCR to evaluate the expression of miR-141-3p in endometrial samples. In addition, western blot analysis was used to assess the expression of Krüppel-like factor 12 (KLF-12). The proliferation and migration of ectopic endometrial stromal cells (ESCs) were determined by MTT assay and Transwell assay, respectively. Cell apoptosis was evaluated using a Cell Death Detection ELISA Plus kit. The results showed that miR-141-3p and KLF-12 were significantly different in paired ectopic and eutopic endometrial samples. miR-141-3p overexpression significantly restrained the proliferation and migration and promoted the apoptosis of ectopic ESCs, whereas a decreased level of miR-141-3p was associated with opposite results. Furthermore, dual-luciferase reporter assay confirmed that KLF-12 was a novel target of miR-141-3p, while it also decreased the effects of miR-141-3p on the proliferation, apoptosis, and migration of ectopic ESCs. Our data suggested that enhanced expression of miR-141-3p suppressed the proliferation and migration of ectopic ESCs and promoted their apoptosis via targeting KLF-12. Our results may provide a novel potential therapeutic target for the treatment of endometriosis.
PMID: 31129698 [PubMed – as supplied by publisher]
https://academic.oup.com/humrep/advance-article-abstract/doi/10.1093/humrep/dez067/5497425?redirectedFrom=fulltext
https://www.ncbi.nlm.nih.gov/pubmed/31119261?dopt=Abstract
Related Articles
Peroxisome proliferator-activated receptor-γ coactivator 1α-mediated pathway as a possible therapeutic target in endometriosis.
Hum Reprod. 2019 May 23;:
Authors: Kataoka H, Mori T, Okimura H, Matsushima H, Ito F, Koshiba A, Tanaka Y, Akiyama K, Maeda E, Sugahara T, Tarumi Y, Kusuki I, Khan KN, Kitawaki J
Abstract
STUDY QUESTION: Is a peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-mediated pathway involved in the development of endometriosis?
SUMMARY ANSWER: PGC-1α plays critical roles in inflammation and cell proliferation of endometriotic tissues and may be involved in the development of endometriosis.
WHAT IS KNOWN ALREADY: Expression levels of PGC-1α are higher in ovarian endometrioma (OE) than normal endometrium (NE). PGC-1α also stimulates aromatase activity and promotes local estrogen biosynthesis in OE.
STUDY DESIGN, SIZE, DURATION: This is a case-controlled biological study using endometrial cells and tissues derived from 23 women with, and 10 women without, OE.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Ectopic endometriotic and eutopic endometrial stromal cells (SCs) were isolated and maintained in culture. PGC-1α was either overexpressed in the cells or knocked down using siRNA. The expression of PGC-1α and other factors during endometriosis was examined using real-time PCR and western blotting, cell proliferation was measured using Cell Counting Kit-8 (WST-8) assays and transcriptional activity was assessed using luciferase reporter assays.
MAIN RESULTS AND THE ROLE OF CHANCE: PGC-1α overexpression promoted the proliferation of OESCs in a time-dependent manner (P < 0.01 versus control) but not NESCs. PGC-1α stimulated aromatase (P < 0.01 versus control) and interleukin (IL)-6/IL-8 mRNA expression levels (P < 0.05 versus control for each) and led to inhibitor kappa B phosphorylation protein expression and upregulation of the apoptosis inhibitors X-linked inhibitor of apoptosis protein and survivin at mRNA level (P < 0.05 versus control for each). HX531, a selective retinoid-X receptor-α (RXRα) antagonist, suppressed the PGC-1α-induced cell proliferation (P < 0.05 versus control), aromatase/IL-6/IL-8/survivin mRNA expression (P < 0.05 versus control for each) and transcription reporter activity of PGC-1α in a dose-dependent manner (P < 0.01 versus control). Moreover, HX531 downregulated PGC-1α-induced aromatase-promoter PI.3-II transcripts in OESCs, and PGC-1α knockdown reduced aromatase, IL-6/IL-8 and antiapoptotic factors mRNA expression (P < 0.05 versus control for each). Notably, the Histogram score, which was used for quantifying RXRα status, was markedly higher in OE than in NE tissue (P < 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only OE tissues were included in this study, while peritoneal and deep infiltrating endometriotic tissues were not. Therefore, these findings might not be generalized to other types of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: In OESC, PGC-1α stimulated cell proliferation and was involved in local estrogen biosynthesis, inflammation and apoptosis, and these effects of PGC-1α were inhibited by HX531. The suppression of PGC-1α-induced proliferation by HX531 in OESCs but not NESCs suggests that the PGC-1α-RXRα axis could play critical roles in promoting endometriosis. This is the first report of a relationship between PGC-1α and inhibitor of apoptosis proteins in endometriosis. Based on these findings, the PGC-1α-mediated pathway could represent a potential target in molecular therapy of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The study is supported in part by Grants-in-Aid for Scientific Research (15 K10681 and 15 K10726) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan). The authors have no conflicts of interest to disclose. PMID: 31119261 [PubMed - as supplied by publisher]
https://www.medicalnewstoday.com/articles/325249.php
