Proposal for targeted, neo-evolutionary-oriented, secondary prevention of early-onset endometriosis and adenomyosis. Part I: pathogenic aspects

Human Reproduction, Journal Year: 2023, Volume and Issue: 39(1), P. 1 - 17

Published: Nov. 10, 2023

Abstract The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, prolonged periods of lactational amenorrhoea. For hundreds thousands years, menstruators experienced few ovulatory cycles, even though they were genetically adapted ovulate menstruate every month. In post-industrial menarche gradually declined, birth progressively increased, breastfeeding became optional often short duration. This created mismatch between genetic adaptation socio-environmental evolution, so that what was initially probable reproductive subsequently contributed increased susceptibility diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial breast cancer and, hypothetically, also those number menstruations, endometriosis adenomyosis. incidence shows steep progressive increase around 25 but given consistently reported delay in diagnosis, actual curve should be shifted left, supporting possibility disease has its roots adolescence. raises question whether, from an evolutionary point view, anovulation amenorrhoea not still considered physiological state, especially postmenarchal period. However, frequency recent decades been demonstrated, although this deserves further epidemiological investigation. addition, occurs minority individuals exposed retrograde menstruation, other important pathogenic factors scrutinised. Research resumed explore more detail transtubal reflux only blood, cells, whether are systematically present peritoneal fluid after menstruation. If repetitive early years shown risk adenomyosis development progression susceptible individuals, hormonal interventions could used secondary prevention symptomatic adolescents.

Language: Английский

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The pathogenesis of endometriosis and adenomyosis: insights from single-cell RNA sequencing

Biology of Reproduction, Journal Year: 2024, Volume and Issue: 110(5), P. 854 - 865

Published: Feb. 22, 2024

Abstract Endometriosis and adenomyosis are two similar gynecological diseases that characterized by ectopic implantation the growth of endometrial tissue. Previous studies have reported they share a common pathophysiology in some respects, such as cellular composition resistance to progestogen lesions, but their underlying mechanisms remain elusive. Emerging single-cell ribonucleic acid sequencing (scRNA-seq) technologies allow for dissection transcriptome mapping reveal etiology at level individual cell. In this review, we summarized published findings research on scRNA-seq regarding components molecular profiles diverse lesions. They show epithelial cell clusters may be vital progenitors endometriosis adenomyosis. Subclusters stromal cells, mesenchymal stem cells fibroblasts, also involved occurrence adenomyosis, respectively. Moreover, CD8+ T natural killer macrophages exhibit deficiency clearing immune microenvironment endometriosis. It seems responses activated Understanding characteristics still needs further exploration. Finally, discuss application from clinical diagnosis treatment. This review provides fresh insights into pathogenesis well therapeutic targets level.

Language: Английский

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Endometriosis and adenomyosis: Similarities and differences

Best Practice & Research Clinical Obstetrics & Gynaecology, Journal Year: 2023, Volume and Issue: 92, P. 102432 - 102432

Published: Dec. 5, 2023

Deep endometriosis and uterine adenomyosis are two frequently encountered conditions affecting approximately 200 million women worldwide. They closely related, showing similar histological patterns multiple common pathogenic features, share the same symptoms. It is therefore not surprising that they often thought to have a developmental origin. Indeed, both deep appear derive from estrogen-dependent overproliferation of endometrial tissue its subsequent implantation in ectopic sites. Although scientific community has shown increasing interest these diseases over recent years, neither pathogenesis yet been elucidated, so there currently no efficient treatment options. Understanding mechanisms underlying disease development, as well discerning their relationship, key improving clinical management for millions patients. The aims this review summarize current knowledge on pathogeneses discuss possibility entities actually differential phenotypes disease.

Language: Английский

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Is retrograde menstruation a universal, recurrent, physiological phenomenon? A systematic review of the evidence in humans and non-human primates

Human Reproduction Open, Journal Year: 2024, Volume and Issue: 2024(3)

Published: Jan. 1, 2024

What are the quantitative, qualitative, and temporal patterns of retrograde mentruation?

Language: Английский

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TET3-overexpressing macrophages promote endometriosis

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(21)

Published: Aug. 14, 2024

Endometriosis is a debilitating, chronic inflammatory disease affecting approximately 10% of reproductive-age women worldwide with no cure. While macrophages have been intrinsically linked to the pathophysiology endometriosis, targeting them therapeutically has extremely challenging due their high heterogeneity and because these disease-associated (DAMs) can be either pathogenic or protective. Here, we report identification characterized by TET3 overexpression in human endometriosis lesions. We show that factors from microenvironment upregulated expression, transforming into DAMs. stimulated proinflammatory cytokine production via feedback mechanism involving inhibition let-7 miRNA expression. Remarkably, cells relied on for survival hence were vulnerable knockdown. demonstrated Bobcat339, synthetic cytosine derivative, triggered degradation both mouse macrophages. This was dependent von Hippel-Lindau (VHL) E3 ubiquitin ligase whose expression also TET3-overexpressing Furthermore, depleting through myeloid-specific Tet3 ablation using Bobcat339 strongly inhibited progression mice. Our results defined as key contributors attractive therapeutic targets endometriosis. findings may applicable other diseases where DAMs important roles.

Language: Английский

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Are Adenomyosis and Endometriosis Phenotypes of the Same Disease Process?

Biomolecules, Journal Year: 2023, Volume and Issue: 14(1), P. 32 - 32

Published: Dec. 25, 2023

In recent literature reviews, we concluded that the possibility endometrial molecular aberrations are sole or a necessary determinant of endometriosis and Tissue Injury Repair (TIAR) theory yet to be convincingly proven. Here, critically examine adenomyosis represent different phenotypes single disease. A common etiopathology for has been suggested because both conditions entail presence tissue at locations other than lining uterus. There wide differences in reported disease incidence prevalence and, consequently, estimates coexistence conditions. some similarities but also their clinical features predisposing factors. Each condition range subtypes. These alone pose question whether subtypes have etiopathologies, turn, this raises they all share etiology. It is debatable recognized between eutopic endometrium compared those unaffected women cause effect The finding mutations, particularly KRAS, lend support notion shared factors, insufficient evidence causation.

Language: Английский

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Epidemiology of endometriosis in Kazakhstan: a national population-based cohort analysis (2014–2019) using data from the national electronic healthcare system

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 7, 2025

Endometriosis is a condition affecting reproductive-age women and associated with dysmenorrhea, pelvic organs dysfunction, pain, infertility. The real epidemiology of endometriosis remains underestimated. No data are available on prevalence in Kazakhstan. Therefore, the aim this was to investigate epidemiology, complications, surgical management approach, outcomes Kazakhstan by analyzing large-scale Kazakhstani healthcare from Unified Nationwide Electronic Health System (UNEHS). A population-based study among treated any setting Republic during period 2014-2019 performed. International Classification Diseases (ICD) 10th edition used retrieve ("N80" "N97"). ICD 9th edition's procedural codes were utilized information procedures performed manage patients endometriosis. In total, 7,682 records diagnosed analyzed all regions. overall female population 0.12%, 50.1% them suffering uterus, 34.5% ovarian endometriosis, 9.5% peritoneum. most affected group (25-44 years old). rates higher 35-39, 40-44, 45-49 old age groups - 0.4 per 1000 corresponding age. common for laparoscopic cystectomy closed biopsy 16.4 13.5%, respectively. Among registered cases prevalent condition. However, analysis UNEHS reveals incomplete inconsistent registration disease, which results underestimation disease's burden. Clinical specialist health authorities must work ensure proper diagnosis end improve disease outcomes.

Language: Английский

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Hormone receptor profile of ectopic and eutopic endometrium in adenomyosis: a systematic review

Human Reproduction Open, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Abstract STUDY QUESTION What is the hormone receptor profile of adenomyosis lesions in comparison to correctly located endometrium? SUMMARY ANSWER Adenomyosis exhibit increased oestrogen (ER) expression compared eutopic endometrium; there are conflicting results regarding progesterone (PR) and a lack studies on androgen (AR) expression. WHAT IS KNOWN ALREADY express receptors indicating an influence from ovarian steroid hormones. However, treatments often ineffective controlling symptoms, which suggests alternate hormonal responses and, potentially, distinct within endometrium. DESIGN, SIZE, DURATION This systematic review with thematic analysis retrieved PubMed, Ovid Medline, Embase, Scopus, Cochrane Library databases, searches were conducted inception through May 2024. Human included identified using combination exploded MeSH terms (‘adenomyosis’) free-text search (‘oestrogen receptor’, ‘progesterone ‘androgen ‘hormone receptor’). PARTICIPANTS/MATERIALS, SETTING, METHODS was reported accordance PRISMA guidelines. All reporting original data concerning endometrium included. Studies that did not report or provide field excluded. Bias completed for each study Newcastle–Ottawa scoring system. MAIN RESULTS AND THE ROLE OF CHANCE There 1905 identified, screened include 12 met eligibility criteria, including 11 proteomic one transcriptional study, total 555 individual participants. ER consistently endometrium, specifically secretory phase. When endometrial subregion considered, this difference specific functionalis only. different isoforms increase ERα rather than ERβ. PR expression, most showing no significant reduced levels paucity AR lesions, only small sample size LIMITATIONS, REASONS FOR CAUTION A high risk bias arose grouping samples across menstrual cycle phases analysis. The coexistence gynecological conditions like endometriosis may also confound Most employing immunostaining comment region-specific differences Given well-documented cyclical variations need more attention represents notable limitation current body literature. WIDER IMPLICATIONS FINDINGS highlights dominance elevated agrees literature suggesting local hyper-oestrogenism lesions. Heterogeneity timing region specificity prevent conclusions resistance study. Future investigations should minimize well-defined cohorts, leading robust exploration profiles identify therapeutic targets deepen our understanding pathogenesis. FUNDING/COMPETING INTEREST(S) work supported by Wellbeing Women Research Project grants RG1073 RG2137 (D.K.H.), Entry-Level Scholarship ELS706 Medical Council grant MR/V007238/1 (A.M. D.K.H.), as well University Liverpool (L.T.). conflicts interest. HROPEN-24-0294.R2 protocol published PROSPERO Register Systematic Reviews 27 September 2023, registration number CRD4202346.

Language: Английский

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Real world perspectives on endometriosis disease phenotyping through surgery, omics, health data, and artificial intelligence

npj Women s Health, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 6, 2025

Endometriosis is an enigmatic disease whose diagnosis and management are being transformed through innovative surgical, molecular, computational technologies. Integrating single-cell other omic data with clinical surgical metadata can identify multiple subtypes translation to novel diagnostics therapeutics. Herein, we present real-world perspectives on endometriosis the importance of multidisciplinary collaboration in informing epidemiologic, cell-specific contexts.

Language: Английский

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A “novel” MRI sequence for improving conspicuity and detection of hemorrhagic foci in pelvic endometriosis: Technical note

European Journal of Radiology, Journal Year: 2025, Volume and Issue: 185, P. 112007 - 112007

Published: Feb. 17, 2025

Language: Английский

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