Immune Dysregulation in Endometriomas: Implications for Inflammation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4802 - 4802

Published: April 28, 2024

The most common manifestation of endometriosis, a condition characterized by the presence endometrial-like tissue outside uterus, is endometrioma, cystic ovarian lesion. It commonly occurring associated with chronic pelvic pain exacerbated prior to and during menstruation, as well infertility. exact pathomechanisms endometrioma are still not fully understood. Emerging evidence suggests pivotal role immune dysregulation in pathogenesis endometriomas, primarily influencing both local systemic inflammatory processes. Among factors implicated creation milieu alterations serum levels several cytokines stand out, including IL-6, IL-8, IL-1β, along abnormalities innate system. While numerous signaling pathways have been suggested play process linked only NF-κB has conclusively demonstrated be involved. Additionally, increased oxidative stress, resulting from contributing identified primary driver inflammation condition. This article reviews current understanding dysfunctions their implications for inflammation.

Language: Английский

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The role of regulatory T-cells in the development of endometriosis

Human Reproduction, Journal Year: 2024, Volume and Issue: 39(7), P. 1367 - 1380

Published: May 16, 2024

Abstract Endometriosis is a benign disease of the female reproductive tract, characterized by process chronic inflammation and alterations in immune response. It estimated to affect 2–19% women general population commonly associated with symptoms pelvic pain infertility. Regulatory T cells (Treg) are subpopulation lymphocytes that potent suppressors inflammatory response, essential preventing destructive immunity all tissues. In endometriosis, several studies have investigated possible role Treg development disease. Most date heterogeneous methodology based on small number cases, which means it impossible define their exact at present. Based current knowledge, seems disturbed homeostasis, leading increased systemic local within ectopic eutopic endometrium, present who eventually develop endometriosis. also evident different subsets human roles suppressing Recent patients endometriosis naive/resting FOXP3lowCD45RA+ cells, upon cell receptor stimulation, differentiate into activated/effector FOXP3highCD45RA− strong immunosuppressive activity. addition, critical factors controlling expression Treg/effector genes, including reactive oxygen species heme-responsive master transcription factor BACH2, were found be upregulated endometriotic lesions. As shown recently for cancer microenvironments, microbial may contribute composition FOXP3+ subpopulations Furthermore, cytokines, such as IL-7, control homeostasis through tyrosine phosphorylation STAT5 signalling pathway, been dysregulated. To better understand future should use clear definitions Tregs along specific characterization non-Treg (FOXP3lowCD45RA−) fraction, itself mixture follicular producing cytokines.

Language: Английский

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Iron metabolism markers in peritoneal fluid of patients with endometriosis: systematic review and meta-analysis

Journal of Endometriosis and Uterine Disorders, Journal Year: 2024, Volume and Issue: 5, P. 100061 - 100061

Published: Jan. 5, 2024

The purpose of this systematic review and meta-analysis was to determine iron metabolism markers in the peritoneal fluid (PF) women with endometriosis. Search conducted electronic databases including PubMed, Cochrane Library, Google Scholar, ClinicalTrials.gov, Scopus, Embase. Clinical trials that reported original data concerning determination content reproductive age or without endometriosis were included. 16 studies included for qualitative analysis. We have three meta-analyses: ferritin concentrations PF statistically significantly higher group (p = 0.01 p 0.007, respectively); lactoferrin levels not different between groups 0.2). According our results, patients tend increased such as PF. Therefore, these may be used future a diagnostic tool. Understanding roles pathogenesis could inform research, potentially leading more effective treatments diagnostics disease.

Language: Английский

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Oxidative Stress and the Nrf2/PPARγ Axis in the Endometrium: Insights into Female Fertility

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1081 - 1081

Published: June 22, 2024

Successful pregnancy depends on precise molecular regulation of uterine physiology, especially during the menstrual cycle. Deregulated oxidative stress (OS), often influenced by inflammatory changes but also environmental factors, represents a constant threat to this delicate balance. Oxidative induces reciprocally regulated nuclear factor erythroid 2-related 2/peroxisome proliferator-activated receptor-gamma (Nrf2/PPARγ) pathway. However, increased PPARγ activity appears be double-edged sword in endometrial physiology. Activated attenuates inflammation and OS restore redox homeostasis. it interferes with physiological processes cycle, such as hormonal signaling angiogenesis. This review provides an elucidation mechanisms that support interplay between OS. Additionally, offers fresh perspectives Nrf2/PPARγ pathway concerning receptivity its potential implications for infertility.

Language: Английский

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Update on the pathogenesis of endometriosis-related infertility based on contemporary evidence

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 10, 2025

Endometriosis, the most prevalent cause of infertility, is associated with anatomical distortion leading to adhesions and fibrosis, as well endocrine abnormalities immune disorders. This review discusses mechanisms underlying endometriosis-related infertility. Firstly, alterations in hypothalamic-pituitary-ovarian axis lead secretion gonadotropins steroid hormones, adverse effects on ovulation implantation, fertility decline. Secondly, dysregulation hypothalamic-pituitary-adrenal induces elevated serum cortisol prolactin levels patients endometriosis, accounting for its regulation stress, depression, anxiety. Abnormal interactions between endometrial cells system change local microenvironment, resulting epithelial-mesenchymal transition inflammation. Activated epithelial cells, stromal immunocytes produce various chemokines, cytokines, or autoantibodies, creating an unfavorable environment embryo implantation. These findings suggest that spectrum play a crucial role Thirdly, oxidative stress has ovarian reserve subsequent embryonic development, predicting another promising strategy An unbalanced redox state, including impaired mitochondrial function, dysregulated lipid metabolism, iron-induced generates pro-oxidative which negatively impacts oocyte quality sperm viability. Thus, updated understanding involved this disease will help develop effective strategies manage

Language: Английский

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Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions

Human Reproduction, Journal Year: 2023, Volume and Issue: 39(1), P. 18 - 34

Published: Nov. 10, 2023

According to consistent epidemiological data, the slope of incidence curve endometriosis rises rapidly and sharply around age 25 years. The delay in diagnosis is generally reported be between 5 8 years adult women, but it appears over 10 adolescents. If this true, actual onset many young women would chronologically placed early postmenarchal Ovulation menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour development adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche not only an indicator ensuing or adenomyosis, also promote transition from chronic pelvic pain through central sensitization mechanisms, as well overlapping conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, preserving future reproductive potential should focused on group that could benefit most intervention, i.e. severely symptomatic Early-onset adenomyosis promptly suspected even physical ultrasound findings negative, long-term ovulatory suppression established until conception seeking. As nowadays mean using hormonal therapies several drug safety evaluation crucial. In adolescents without recognized major contraindications oestrogens, use very low-dose combined oral contraceptives associated with a marginal increase individual absolute risk thromboembolic events. Oral containing oestradiol instead ethinyl further limit such risk. Oral, subcutaneous, intramuscular progestogens do risk, interfere attainment peak bone mass women. Levonorgestrel-releasing intra-uterine devices safe alternative adolescents, amenorrhoea frequently induced ovarian activity. With regard oncological net effect oestrogen-progestogen combinations small reduction overall cancer Whether surgery considered first-line approach symptoms seems questionable. Especially large endometriomas infiltrating lesions detected imaging, laparoscopy reserved who refuse treatments whom medications effective, tolerated, contraindicated. Diagnostic therapeutic algorithms, including self-reported outcome measures, individuals clinical suspicion early-onset proposed.

Language: Английский

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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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Regulated Cell Death in Endometriosis

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 142 - 142

Published: Jan. 23, 2024

Regulated cell death (RCD) represents a distinct mode of demise, differing from accidental (ACD), characterized by specific signaling cascades orchestrated diverse biomolecules. The regular process plays crucial role in upholding internal homeostasis, acting as safeguard against biological or chemical damage. Nonetheless, programmed deaths have the potential to activate an immune–inflammatory response, potentially contributing diseases enlisting immune cells and releasing pro-inflammatory factors. Endometriosis, prevalent gynecological ailment, remains incompletely understood despite substantial progress unraveling associated pathways. Its complexity is intricately tied dysregulation inflammatory responses, with various RCD processes such apoptosis, autophagic death, pyroptosis, ferroptosis implicated its development. Notably, limited research explores association between endometriosis pathways like pyroptosis cuproptosis. exploration regulated context holds tremendous for further advancements. This article thoroughly reviews molecular mechanisms governed their implications endometriosis. A comprehensive understanding mechanism has catalyze development promising therapeutic strategies chart course future directions field.

Language: Английский

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Mechanisms of Endometrioma-Mediated Ovarian Damage: Myths and Facts

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2147 - 2147

Published: March 21, 2025

Ovarian endometriomas (OEMs), cystic formations within the ovaries, are a significant manifestation of endometriosis and present in 20-40% affected women. Despite extensive research, pathogenesis remains unclear, with retrograde menstruation, coelomic metaplasia, lymphatic dissemination being proposed mechanisms. OEMs negatively impact ovarian function by reducing reserve, disrupting folliculogenesis, altering microenvironment through oxidative stress, inflammation, fibrosis. Elevated reactive oxygen species (ROS) accelerate follicular atresia, extracellular matrix remodeling contributes to damage, while immune dysregulation cytokine imbalances further exacerbate condition. The presence does not significantly affect live birth rates vitro fertilization (IVF) treatments, despite potential reductions quality quantity oocytes. However, their surgical excision compromises reserve. This review highlights complex mechanisms which impair emphasizes need for research develop strategies that mitigate these effects, ultimately improving reproductive outcomes women endometriomas.

Language: Английский

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Spotlight on iron overload and ferroptosis: Research progress in female infertility

Life Sciences, Journal Year: 2023, Volume and Issue: 340, P. 122370 - 122370

Published: Dec. 22, 2023

Language: Английский

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