The Known, the Unknown and the Future of the Pathophysiology of Endometriosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5815 - 5815

Published: May 27, 2024

Endometriosis is one of the most common causes chronic pelvic pain and infertility, affecting 10% women reproductive age. A delay up to 9 years estimated between onset symptoms diagnosis endometriosis. currently defined as presence endometrial epithelial stromal cells at ectopic sites; however, advances in research on endometriosis have some authors believing that should be re-defined “a fibrotic condition which stroma epithelium can identified”. There are several theories etiology disease, but origin remains unclear. This review addresses role microRNAs (miRNAs), naturally occurring post-transcriptional regulatory molecules, endometriotic lesion development, inflammatory environment within peritoneal cavity, including cytokines play during development how animal models helped our understanding pathology this enigmatic disease.

Language: Английский

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Quantification of Free Circulating DNA and Differential Methylation Profiling of Selected Genes as Novel Non-Invasive Biomarkers for Endometriosis Diagnosis

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 69 - 69

Published: Jan. 6, 2025

Endometriosis is a chronic, estrogen-dependent disorder associated with the presence of endometrial cells mainly in pelvic cavity, causing systemic immune inflammation, infertility, epigenetic dysregulation differential DNA methylation, coelomic metaplasia, and pain. It affects approximately 10-12% women. Despite decades research, full pathophysiology, diagnostic roadmap, clinical management strategies for endometriosis are not yet fully elucidated. Cell-free (Cf-DNA) peripheral blood diseased healthy individuals was discovered 1950s. Quantifying Cf-DNA specific methylation group genes have been proposed as potential non-invasive biomarkers somatic constitutional genetics various other pathological disorders. In this study, we investigated levels 78 young women, 38 whom had confirmed via laparoscopy 40 were healthy. We found significant difference between two groups when quantified, 3.9 times more serum women endometriosis. also identified nine target potentially involved pathogenesis endometriosis, different profile groups. Our data suggest that combination cell-free quantification assessment signature can be predictive test

Language: Английский

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Perturbations of the endometrial immune microenvironment in endometriosis and adenomyosis: their impact on reproduction and pregnancy

Seminars in Immunopathology, Journal Year: 2025, Volume and Issue: 47(1)

Published: Feb. 18, 2025

Abstract The impact of endometriosis and adenomyosis on reproduction pregnancy is significant, with both conditions linked to increased rates infertility, poor ovarian function in women endometriosis, elevated complications those adenomyosis. However, the underlying mechanisms remain largely unclear. Both share a similar pathophysiological process characterized by growth ectopic endometrium, which may originate from eutopic endometrium. Notably, surgical removal lesions does not appear significantly improve reproductive outcomes, further underscoring importance endometrium these adverse effects. Emerging evidence indicates substantial differences endometrial NK cells, macrophages, T leading inflammatory responses These alterations contribute only disease progression but also defective receptivity, insufficient angiogenesis remodeling, impaired maternal-fetal immune tolerance, placentation, thereby influencing embryo implantation maintenance. This provides an immunological perspective explain higher infertility observed affected women. Therefore, we systematically review cells compared healthy controls, exploring potential impacts changes pregnancy. aims lay groundwork for future studies immunopathogenesis associated adenomyosis-related failure complications, shedding lights development immunotherapeutic strategies mitigate

Language: Английский

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Integration of Single Cell and Bulk RNA-Sequencing Reveals Key Genes and Immune Cell Infiltration to Construct a Predictive Model and Identify Drug Targets in Endometriosis

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 2783 - 2804

Published: Feb. 1, 2025

Endometriosis is a common chronic neuroinflammatory disease with poorly understood pathogenesis. Molecular changes and specific immune cell infiltration in the eutopic endometrium are critical to progression. This study aims explore mechanisms molecular differences proliferative of endometriosis by integrating bulk RNA-seq single-cell RNA sequencing (scRNA-seq) data, develop diagnostic predictive models for disease. Gene expression profiles from patients healthy controls were obtained Expression Omnibus. Single-cell data processed using R packages, clusters' contributions calculated. Differentially expressed genes (DEGs) intersected significant mesenchymal scRNA-seq, model was constructed LASSO analysis. Key gene explored through Set Enrichment Variation Analyses. miRNA networks transcriptional regulation analyses conducted, potential drugs predicted Connectivity Map database. RT-qPCR validated key expression. Mesenchymal cells identified as major contributors regression eight genes: SYNE2, TXN, NUPR1, CTSK, GSN, MGP, IER2, CXCL12. The based on these achieved AUC values 1.00 0.8125 training validation cohorts. Immune analysis showed increased CD8+ T monocytes patients. Drug target prediction indicated that like Retinol, Orantinib, Piperacillin, NECA negatively correlated endometriosis. aligned bioinformatics Significant transcriptomic altered potentially contribute Our demonstrates high accuracy, offering insights diagnosis treatment strategies.

Language: Английский

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The inconsistent pathogenesis of endometriosis and adenomyosis: insights from endometrial metabolome and microbiome

mSystems, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Endometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue frequently linked with chronic pelvic pain infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed samples from 244 participants, split into 91 EM patients, 56 AM 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) 5R 16S rRNA sequencing to examine metabolome microbiome profiles. Additionally, integrated transcriptomic analysis using nine data sets investigate biological basis these conditions. Metabolomic profiling revealed distinct metabolic microbial signatures. Specific pathways, including linoleic acid glycerophospholipid metabolism, show significant alterations in both Notably, four metabolites, phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes AM, suggesting shared pathological features. Furthermore, taxonomic identified unique bacterial species associated each condition, particularly those belonging phylum Proteobacteria, which correlated altered Machine learning models demonstrated high predictive accuracy for differentiating between EM, HC based on Integrative highlighted pathways related immune response signaling transduction condition. Our study provides fresh insights pathogenesis through a multi-omic approach, potential inconsistencies underlying mechanisms. IMPORTANCE Existing research connection endometriosis (AM), underscoring overlapping symptoms pathophysiological Although role microbiota inflammatory conditions has been acknowledged, comprehensive investigations cases have limited. Previous studies communities conditions; however, they were constrained small sample sizes lack analyses metabolomics. ongoing debate over whether should be classified as separate diseases or phenotypes emphasizes necessity further exploration molecular interactions. uncovers signatures revealing that may contribute pathogenesis. integration offers valuable complex interactions disorders.

Language: Английский

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Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Optimal reproductive success following parturition in lactating dairy cows is dependent upon adequate completion of uterine involution. Failure to resolve pathogenic bacterial contamination within the first week postpartum can lead disease (metritis). Metritis associated with decreased fertility and a failure or delay establish pregnancy. We hypothesized that inflammation resulting from early metritis would be long-term changes morphology due impaired involution 30 days (dpp). First parity Holstein were diagnosed without at 7-10 dpp tissue analyzed (Exp. 1), 80 165 2) for presence abnormal morphology, including invasion endometrial glands stroma into myometrium (adenomyosis) using immunohistochemistry FOXA2 (uterine gland specific marker) late fibrosis mason’s trichrome stain (MTS). Severity adenomyosis was determined by number size adenomyotic foci, distance foci endometrium-myometrium interface (EMI), degree (MTS intensity). The presence, size, EMI greater later diagnosis metritis. Endometrial stratum basalis (at EMI) compared compactum endometrium (near lumen) all Exp. 2 cows, but (regardless region) observed Taken together, these data indicate modifications aberrant increased pathological fibrogenesis, leading (scar tissue). Additionally, collagen fiber suggests correlation between development fibrosis, which could possibly result sustained caused disease.

Language: Английский

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Human Endometrial Pericytes: A Comprehensive Overview of Their Physiological Functions and Implications in Uterine Disorders

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1510 - 1510

Published: Sept. 9, 2024

Pericytes are versatile cells integral to the blood vessel walls of microcirculation, where they exhibit specific stem cell traits. They essential in modulating flow, ensuring vascular permeability, and maintaining homeostasis involved tissue repair process. The human endometrium is a unique complex that serves as natural scar-free healing model with its cyclical regeneration process every month. regulation pericytes has gained increasing attention due their involvement various physiological pathological processes. However, endometrial less well studied compared other organs. This review aims provide comprehensive overview pericytes, focus on elucidating function potential implications uterine disorders.

Language: Английский

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Adenomyosis and fibrosis define the morphological memory of the postpartum uterus of dairy cows previously exposed to metritis.

JDS Communications, Journal Year: 2024, Volume and Issue: 6(2), P. 250 - 255

Published: Oct. 31, 2024

Optimal fertility after calving in lactating dairy cows is dependent upon the successful completion of uterine involution. Invasion pathogenic bacteria into environment within first week postpartum can lead to disease (metritis). Metritis associated with decreased and a failure or delay establishing pregnancy. We hypothesized that early metritis would be long-term changes morphology begin 30 d (DPP) are present during typical breeding window (2-6 mo postpartum). First parity Holstein were diagnosed (M) deemed healthy (H) at 7 10 DPP tissues collected analyzed postmortem (experiment [Exp.] 1; M = 10, H 10), 80 165 (Exp. 2; 9, 10) for presence abnormal morphology, including invasion endometrial glands stroma myometrium (adenomyosis) fibrosis. Glands identified using immunohistochemistry FOXA2 (uterine gland specific marker) fibrosis was Masson's trichrome stain (MTS). The severity adenomyosis assessed by number size adenomyotic foci distance from endometrium-myometrium interface (EMI). degree defined MTS intensity. Data 2-way ANOVA procedure effect on variables size, EMI, A negative binomial regression model used variable number. presence, EMI greater later 2, DPP) 1, previously metritis, suggesting adenomyosis. Endometrial stratum basalis (near EMI) compared compactum endometrium lumen) all Exp. 2 (80 cows. Greater (regardless region) observed controls. Taken together, these data indicate increased pathological fibrogenesis, leading late (scar tissue), aberrant (adenomyosis). Additionally, collagen fiber suggests correlation between development fibrosis, which could result sustained inflammation caused disease.

Language: Английский

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