The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(3), P. 423 - 436

Published: March 1, 2023

Language: Английский

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Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 14, 2023

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside uterine cavity, affects 10% reproductive-age women. Although pathogenesis endometriosis is uncertain, it widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given not all women with develop endometriosis, immune factors have been hypothesized to affect endometriosis. In this review, we demonstrate peritoneal microenvironment, including innate immunity and adaptive immunity, plays a central role Current evidence supports fact cells, such as macrophages, natural killer (NK) dendritic cells (DCs), neutrophils, T B well cytokines mediators, contribute vascularization fibrogenesis endometriotic lesions, accelerating implantation development lesions. Endocrine system dysfunction influences microenvironment through overexpressed estrogen progesterone resistance. light limitations hormonal therapy, describe prospects for potential diagnostic biomarkers nonhormonal therapy based on regulation microenvironment. Further studies are warranted explore available immunological therapeutic strategies

Language: Английский

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An integrated single-cell reference atlas of the human endometrium

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1925 - 1937

Published: Aug. 28, 2024

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors lacked consensus in defining cell types. We introduce Human Endometrial Cell Atlas (HECA), a high-resolution reference atlas (313,527 cells) combining published new transcriptomics datasets 63 women with without endometriosis. HECA assigns identifies previously unreported types, mapped situ using spatial validated independent single-nuclei dataset (312,246 nuclei, donors). In functionalis, we identify intricate stromal-epithelial coordination via transforming growth factor beta (TGFβ) signaling. basalis, define signaling between fibroblasts an epithelial population expressing progenitor markers. Integration large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells macrophages as most likely dysregulated is valuable resource for studying physiology disorders, guiding microphysiological vitro systems development.

Language: Английский

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Pathogenesis of Endometriosis: New Insights into Prospective Therapies

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11700 - 11700

Published: Oct. 28, 2021

Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2–10% women experience this condition during age, 35–50% whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis treatment, other than surgical procedures scans. It difficult to identify the disease at onset, unless symptoms such as infertility and/or pain present. Determining mechanisms involved pathogenesis vital, not only pave way identification, but also management development less invasive successful treatment strategies. cell proliferation, propagation, evasion immunosurveillance, metastasis. This review reports underlying that individually collectively responsible establishment evolution. Treatment endometriosis mainly involves hormone therapies, which may be undesirable have their own repercussions. therefore important devise alternative strategies both effective cause fewer side effects. Use phytochemicals one them. focuses on pharmacological inhibitors can therapeutically investigated terms effects signaling pathways endometriosis.

Language: Английский

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Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†

Biology of Reproduction, Journal Year: 2021, Volume and Issue: 105(1), P. 7 - 31

Published: March 19, 2021

Emerging evidence supports the notion that inflammation fosters development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, growth transcription factors have indisputable roles in establishment maintenance disorders by initiating complex cascades promote proliferation, angiogenesis, lesion progression. The interaction between is orchestrated a plethora factors, sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk diet, vitamin D, immune system. role these not limited to local pathobiology but also extends involve clinical sequelae range from those confined reproductive tract, such as infertility malignancies, systemic complications cardiovascular disease. Enhanced understanding intricate mechanisms this association will introduce us unvisited pathophysiological perspectives guide future diagnostic therapeutic implications aimed at reducing burden disorders. Utilization inflammatory markers, microRNA, molecular imaging adjuncts may be valuable, noninvasive techniques for prompt detection Further, use novel well previously established therapeutics, immunomodulators, hormonal treatments, medications, cyclooxygenase-2 NF-κB inhibitors, can target pathways involved their pathogenesis. In comprehensive review, we aim dissect existing literature on proposed underlying interactions, its contribution sequelae, entails.

Language: Английский

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Endometriosis and polycystic ovary syndrome are diametric disorders

Evolutionary Applications, Journal Year: 2021, Volume and Issue: 14(7), P. 1693 - 1715

Published: May 4, 2021

Evolutionary and comparative approaches can yield novel insights into human adaptation disease. Endometriosis polycystic ovary syndrome (PCOS) each affect up to 10% of women significantly reduce the health, fertility, quality life those affected. PCOS endometriosis have yet be considered as related one another, although both conditions involve alterations prenatal testosterone levels atypical functioning hypothalamic-pituitary-gonadal (HPG) axis. Here, we propose evaluate hypothesis that represent extreme diametric (opposite) outcomes variation in HPG axis development activity, with mediated notable part by low postnatal testosterone, while is high testosterone. This disorder predicts that, for characteristics shaped axis, including hormonal profiles, reproductive physiology, life-history traits, body morphology, will manifest opposite phenotypes. To these predictions, review synthesize existing evidence from developmental biology, endocrinology, history, epidemiology. The phenotypes between strongly supported across diverse fields research. Furthermore, contrasts humans parallel differences among nonhuman animals effects versus on female traits. These findings suggest maladaptive extremes expression sexually dimorphic provides novel, unifying, proximate, evolutionary explanations risk, synthesizes lines research concerning two most common disorders, generates future avenues improving health women.

Language: Английский

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Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1299 - 1299

Published: Sept. 14, 2022

The specific regulation of inflammatory processes by steroid hormones has been actively studied in recent years, especially progesterone (P4) and progestins. mechanisms the anti-inflammatory immunomodulatory P4 action are not fully clear. effects can be defined as nonspecific, associated with inhibition NF-κB COX, well prostaglandin synthesis, or specific, T-cell activation, production pro- cytokines, phenomenon immune tolerance. its derivatives (progestins) also include proliferative signaling pathways antagonistic against estrogen receptor beta-mediated a proinflammatory mitogenic factor. is accomplished through participation (PR) chaperones HSP90, immunophilins FKBP51 FKBP52, which validated targets clinically approved immunosuppressive drugs. HSP90 inhibitors, tacrolimus cyclosporine, manifested, among other factors, due to their formation an active ligand–receptor complex interaction constituent immunophilins. Pharmacological agents such inhibitors restore lost effect glucocorticoids chronic autoimmune diseases. By regulating activity it possible increase decrease hormonal signaling, during development hormone resistance. combined immunophilin suppressors may promising strategy treatment diseases, including endometriosis, stress-related disorders, rheumatoid arthritis, miscarriages. Presumably, receptor- immunophilin-targeted drugs act synergistically, allowing for lower dose each.

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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Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 22, 2022

Endometriosis is defined as the presence of endometrial-like glands and stroma located outside uterine cavity. This common, estrogen dependent, inflammatory condition affects up to 15% reproductive-aged women a well-recognized cause chronic pelvic pain infertility. Despite still unknown etiology endometriosis, much evidence suggests participation epigenetic mechanisms in disease etiopathogenesis. The main rationale based on fact that heritable phenotype changes do not involve alterations DNA sequence are common triggers for hormonal, immunological, disorders, which play key role formation endometriotic foci. Epigenetic regulating T-cell responses, including methylation posttranslational histone modifications, deserve attention because tissue-resident T lymphocytes work concert with organ structural cells generate appropriate immune responses functionally shaped by organ-specific environmental conditions. Thus, failure precisely regulate cell transcription may result compromised immunological integrity an increased risk disorders. coexistence endometriosis autoimmunity well-known occurrence. Recent research results indicate regulatory (Treg) number highly active Tregs macrophages have been found peritoneal fluid from endometriosis. Elimination function imbalance between helper Th1 Th2 types reported endometria endometriosis-associated review aims present state art recognition reprogramming factor pathophysiology context T-cell-related autoimmunity. new potential therapeutic approaches modulation and/or adoptive transfer will also be outlined.

Language: Английский

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Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(9)

Published: Aug. 29, 2023

Endometriosis is a common estrogen-dependent disorder wherein uterine lining tissue (endometrium) found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, infertility. Recent evidence also supports systemic inflammatory component that underlies associated co-morbidities, e.g., migraines cardiovascular autoimmune diseases. Genetics environment contribute significantly to disease risk, explosion of omics technologies, underlying mechanisms symptoms are increasingly being elucidated, although novel effective therapeutics for infertility have lagged behind these advances. Moreover, there stark disparities diagnosis, access care, treatment among persons color transgender/nonbinary identity, socioeconomically disadvantaged populations, adolescents, disturbing low awareness health care providers, policymakers, lay public about endometriosis, which, if left undiagnosed under-treated can lead significant fibrosis, infertility, depression, markedly diminished quality life. This review summarizes endometriosis epidemiology, compelling its pathogenesis, pathophysiology age precision medicine, recent biomarker discovery, therapeutic approaches, issues around reproductive justice marginalized populations this spanning past 100 years. As we enter next revolution biomedical research, rich molecular clinical datasets, single-cell omics, population-level data, well positioned benefit from data-driven research leveraging computational artificial intelligence approaches integrating data predicting response medical surgical therapies, prognosis recurrence.

Language: Английский

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