Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Jan. 23, 2020

Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting approximately 176 million women worldwide. It associated with pelvic pain, infertility and fatigue, has substantial impact on health-related quality of life. defined by the growth endometrial-like tissue outside uterus, typically lining cavity ovaries (known as 'lesions'). Macrophages are complex cells at centre this enigmatic condition; they critical for growth, development, vascularisation innervation lesions well generation pain symptoms. In health, tissue-resident macrophages seeded during early embryonic life vital development homeostasis tissues. adult, under challenge, monocytes recruited from blood differentiate into in tissues where fulfil functions, such fighting infection repairing wounds. The interplay between now forefront macrophage research due to their differential roles disorders. some cancers, tumour-associated comprised that within tumour. These different origins play disease progression. Herein, we review complexities dynamics health explore paradigm disease-modified conditions, normally maintain become modified promote disease. We also interrogate evidence support existence multiple phenotypic populations endometriosis how could be exploited therapy.

Language: Английский

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The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain

Human Reproduction Update, Journal Year: 2021, Volume and Issue: 28(1), P. 92 - 131

Published: Sept. 30, 2021

Endometriosis is a chronic, burdensome condition that historically understudied. Consequently, there lack of understanding the etiology disease and its associated symptoms, including infertility chronic pelvic pain (CPP). development influenced by estrogen metabolism inflammation, which are modulated several factors microbiome estrobolome (the collection genes encoding estrogen-metabolizing enzymes in gut microbiome). Therefore, increasing interest role microbiota endometriosis etiology.To date, no cure for treatment options often ineffective. This manuscript will review potential relationship between endometriosis, CPP highlight available data on relation to related symptoms. The overarching goal this inform future research lead deeper possible diagnostic modalities treatments. impact regulation estrobolome, as well inflammation other endometriosis-promoting mechanisms within genital tract, be reviewed. methodological limitations microbiome-related studies critically assessed provide improved guidelines clinical studies.PubMed databases were searched using following keywords: AND microbiome, IVF (in-vitro fertilization) infertility. Clinical preclinical animal trials eligible review, or included. All manuscripts published 2002-2021.In total, 28 6 included review. In both human studies, bacteria enriched groups, although was clear consensus specific compositions with endometriosis. However, bacterial vaginosis-associated Lactobacillus depletion cervicovaginal majority (23/28) studies. Interpretation endometrial limited owing variety factors, discussed addition, metadata outlining antibiotic usage, age, race/ethnicity, menopausal status timing sample diagnosis not consistently reported. Animal (6/6) support bidirectional onset progression.There evidence dysbiotic multiple gynecologic conditions, mounting supporting an association These microbiomes likely play gut-brain axis, further supports putative spectrum symptoms CPP. Collectively, highlights demand more rigorous transparent methodology controls, consistency across field, inclusion key demographic characteristics comparison participants. Rigorous study designs allow better disorders female reproductive tract.

Language: Английский

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The Main Theories on the Pathogenesis of Endometriosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4254 - 4254

Published: Feb. 21, 2023

Endometriosis is a complex disease, which defined by abnormal growth of endometrial tissue outside the uterus. It affects about 10% women reproductive age all over world. causes symptoms that notably worsen patient’s well-being—such as severe pelvic pain, dysfunction organs cavity, infertility and secondary mental issues. The diagnosis endometriosis quite often delayed because nonspecific manifestations. Since disease was defined, several different pathogenetic pathways have been considered, including retrograde menstruation, benign metastasis, immune dysregulation, coelomic metaplasia, hormonal disbalance, involvement stem cells alterations in epigenetic regulation, but true pathogenesis remains poorly understood. knowledge exact mechanism origin progression this significant for appropriate treatment. Therefore, review reports main theories based on current studies.

Language: Английский

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Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review

Medicinal Research Reviews, Journal Year: 2021, Volume and Issue: 41(4), P. 2489 - 2564

Published: May 5, 2021

Abstract Endometriosis (EM) is defined as endometrial tissues found outside the uterus. Growth and development of endometriotic cells in ectopic sites can be promoted via multiple pathways, including MAPK/MEK/ERK, PI3K/Akt/mTOR, NF‐κB, Rho/ROCK, reactive oxidative stress, tumor necrosis factor, transforming growth factor‐β, Wnt/β‐catenin, vascular endothelial estrogen, cytokines. The underlying pathophysiological mechanisms include proliferation, apoptosis, autophagy, migration, invasion, fibrosis, angiogenesis, inflammation, immune escape. Current medical treatments for EM are mainly hormonal symptomatic, thus new, effective, safe pharmaceuticals targeting specific molecular signaling pathways needed. Here, we systematically reviewed literature focused on that specifically target involved pathophysiology EM. Potential drug targets, their upstream downstream molecules with key aberrant signaling, regulatory promoting were discussed. Hormonal pharmaceuticals, melatonin, exerts proapoptotic regulating matrix metallopeptidase activity while nonhormonal pharmaceutical sorafenib antiproliferative effect MAPK/ERK pathway antiangiogenesis VEGF/VEGFR pathway. N‐acetyl cysteine, curcumin, ginsenoside exert antioxidant anti‐inflammatory effects radical scavenging activity. Natural products have high efficacy minimal side effects; example, resveratrol epigallocatechin gallate targets provide synergistic to resolve complexity EM, showing promising treating Although new currently being developed, more detailed pharmacological studies large sample size clinical trials needed confirm safety these near future.

Language: Английский

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The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 25, 2023

Endometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6-10% of all reproductive-aged women. condition in which endometrial tissue, normally lines the inside uterus, deposits other tissues. The etiology pathogenesis endometriosis remain ambiguous. Despite debates, it generally agreed chronic inflammatory disease, patients with appear to be hypercoagulable state. coagulation system plays important roles hemostasis responses. Therefore, purpose this study use publicly available GWAS summary statistics examine causal relationship between factors risk endometriosis.To investigate endometriosis, two-sample Mendelian randomization (MR) analytic framework was used. A series quality control procedures were followed order select eligible instrumental variables strongly associated exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, plasmin). Two independent cohorts European ancestry used: UK Biobank (4354 cases 217,500 controls) FinnGen (8288 68,969 controls). We conducted MR analyses separately FinnGen, by meta-analysis. Cochran's Q test, MR-Egger intercept leave-one-out sensitivity used assess heterogeneities, horizontal pleiotropy, stabilities SNPs endometriosis.Our analysis 11 suggested reliable effect genetically predicted plasma ADAMTS13 level on decreased risk. negative positive vWF observed FinnGen. In meta-analysis, associations remained significant strong size. also identified potential effects different sub-phenotypes endometrioses.Our based data from large-scale population studies demonstrated ADAMTS13/vWF endometriosis. These findings suggest these are involved development may represent therapeutic targets for management disease.

Language: Английский

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Endometriosis and autoimmunity

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 103752 - 103752

Published: Jan. 1, 2025

Language: Английский

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Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions

Cell Genomics, Journal Year: 2025, Volume and Issue: 5(1), P. 100737 - 100737

Published: Jan. 1, 2025

Highlights•Single-cell and spatial data reveal hierarchical microenvironment in endometriomas•Ectopic endometrial stromal cells retain menstrual cycle gene expression patterns•Distinct ovarian (OSCs) links to fibrosis inflammation lesions•WNT5A signaling mediates interactions between ectopic OSCsSummaryEndometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting attachment the local sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell transcriptomic profiling lesions eutopic endometrium endometriosis. We found that (EnS) retained cyclical patterns their counterparts while exhibiting unique contributes pathogenesis identified two distinct localized at different zones lesion, showing differential profiles associated inflammation, respectively. also WNT5A upregulation aberrant activation non-canonical WNT may contribute establishment, offering novel targets for intervention. These will enhance our understanding mechanisms underlying endometriosis paves way developing non-hormonal treatments.Graphical abstract

Language: Английский

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Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 11

Published: Jan. 11, 2021

Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands stroma outside uterine cavity. Ovaries pelvic peritoneum are most common locations for ectopic tissue, followed deep infiltrating EM sites. The cyclic recurrent bleeding, progressive fibrosis peritoneal adhesions glands, may cause different symptoms depending on origin involved. frequent clinical condition affecting around 10% women mainly reproductive age, as well in post-menopausal adolescents, especially with anomalies. risk developing depends complex interaction between genetic, immunological, hormonal, environmental factors. It largely considered to arise due dysfunction immunological surveillance. In fact, exhibit altered functions macrophages, lymphocytes natural killer cells, levels inflammatory mediators growth factors fluid. patients, macrophages preponderant highly active compared healthy women. Peritoneal able regulate events that determine production cytokines, prostaglandins, complement components. Several studies have shown alteration regulation activation, leading inflammation characteristic EM. Aberrant regulation/activation system has been observed cavity affected Thus, inhibition represent new approach treatment EM, given number inhibitors under pre-clinical development. Such an intervention provide broader therapeutic control complement-mediated damage patients. This review will focus our current understanding role activation possible modalities available complement-based therapy.

Language: Английский

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Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

Theranostics, Journal Year: 2021, Volume and Issue: 11(7), P. 3512 - 3526

Published: Jan. 1, 2021

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown regeneration under the control ovarian hormones. Knowledge normal endometrial physiology, as it pertains to regulation menstruation, is essential understand disorders menstruation. Accumulating evidence indicates that autophagy endometrium, hormones, can result infiltration immune cells, which plays an indispensable role endometrium shedding, tissue repair prevention infections during In addition, abnormal levels, together with resulting dysregulated system function, are associated pathogenesis progression endometriosis. Considering its potential value target for treatment menstrual-related endometrium-related disorders, we review activity function menstrual cycles. The estrogen/progesterone-autophagy-immunity axis endometriosis also discussed.

Language: Английский

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Endometriosis: A Disease with Few Direct Treatment Options

Molecules, Journal Year: 2022, Volume and Issue: 27(13), P. 4034 - 4034

Published: June 23, 2022

Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside pelvic cavity. The evolution disease can lead to infertility in addition high treatment costs. Currently, available medications are only effective treating endometriosis-related pain; however, it not targeted treatment. objective this work review characteristics disease, diagnostic means treatments available, as well discuss new therapeutic options.

Language: Английский

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