Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity

Cell Death and Disease, Год журнала: 2022, Номер 13(7)

Опубликована: Июль 4, 2022

Abstract Endometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload ovarian follicular fluid (FF) patients EMs, this condition is associated maturation disorder. However, the underlying molecular mechanism remains largely unknown. In present study, we identified ferroptosis granulosa cells failure EMs based on a retrospective review vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes infertile EMs. Mouse were treated patients' (EMFF) vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, transmission electron microscopy used to assess ferroptosis. effects exosomes examined by nanoparticle tracking RNA-seq, analysis. Finally, therapeutic values vitamin E iron chelator (deferoxamine mesylate) vivo evaluated an model. Patients experienced poorer fertility than non-ovarian We observed that EMFF overload-induced cell vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved process. Notably, undergoing further suppressed releasing from cells. studies, chelators effectively alleviated models. Our study indicates novel through which induces dysmaturity infertility, providing potential strategy for

Язык: Английский

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The emerging role of ferroptosis in female reproductive disorders

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115415 - 115415

Опубликована: Сен. 4, 2023

Iron, as an essential trace element for the organism, is vital maintaining organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis a novel form of programmed cell death distinguished by overload lipid peroxidation, which unique from autophagy, apoptosis necrosis, more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis associated with development female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), cancer (OC), preeclampsia (PE) spontaneous abortion (SA). Pathways genes may participate in processes regulate granulosa proliferation secretion, oocyte development, reserve function, early embryonic placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates occurrence research progress FRDs, view to providing literature references clinical targeting -related pathways regulatory factors management FRDs.

Язык: Английский

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Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature

Diagnostics, Год журнала: 2024, Номер 14(3), С. 312 - 312

Опубликована: Янв. 31, 2024

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments come multiple side effects high recurrence rates for both disease pain. These reasons why exploring possibility of involvement pro-inflammatory anti-inflammatory molecules in process appearance endometriosis. Cytokines play an important role progression endometriosis, influencing cell proliferation differentiation. Pro-inflammatory found intrafollicular fluid. They have impact on number mature optimal-quality oocytes. affects fertility, endometriosis embryo transfer during vitro fertilization (IVF) being investigated several studies. Furthermore, reciprocal influence between cytokines their pathogenesis has been assessed. Today, can affirm roles survival, growth, differentiation, invasion, angiogenesis, immune escape, provides perspective approaching future clinical implications be used as biomarkers or therapy.

Язык: Английский

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Endometriosis and autoimmunity

Autoimmunity Reviews, Год журнала: 2025, Номер unknown, С. 103752 - 103752

Опубликована: Янв. 1, 2025

Язык: Английский

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Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach

Antioxidants, Год журнала: 2022, Номер 11(8), С. 1504 - 1504

Опубликована: Июль 31, 2022

Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation overload. Recent reports shown at the cellular organism levels prevent an inflammatory storm cancer development. Emerging evidence suggests potential mechanisms system Xc-, glutathione peroxidase 4 (GPX4), peroxidation, (GSH), chelators) are involved ferroptosis, which may mediate biological processes such as oxidative stress overload treat cancer. To date, there least three pathways cells: Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, ATG5/ATG7/NCOA4. Here, we summarize recent advances occurrence development context cancer, associations between various modulators, therapeutic strategies targeting for treatment

Язык: Английский

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The role of iron in the pathogenesis of endometriosis: a systematic review

Human Reproduction Open, Год журнала: 2023, Номер 2023(3)

Опубликована: Янв. 1, 2023

What is the role of iron in pathophysiology endometriosis?Iron excess demonstrated wherever endometriotic tissues are found and associated with oxidative stress, an inflammatory micro-environment, cell damage; iron-mediated stress independently linked to subfertility, symptom severity, malignant transformation.Iron tissues, multiple mechanisms have been studied posited explain this. It clear that plays a vital promoting damage. The evidence base large, but no comprehensive reviews exist summarize our understanding highlight overarching themes further suggest future directions study for field.This systematic review thematic analysis retrieved studies from PubMed, Embase, Web Science, Cochrane Library databases searches were conducted inception through August 2022. Human animal published English language included identified using combination exploded MeSH terms ('Iron' 'Endometriosis') free-text search ('Iron', 'Ferric', 'Ferrous', 'Endometriosis', 'Endometrioma').This was reported accordance PRISMA guidelines. All reporting original data concerning or complexes endometriosis included. Studies did not report provided field excluded. Bias completed each by Newcastle-Ottawa scoring system.There 776 records these screened down 53 which met eligibility criteria, including 6 47 human studies, 3556 individual participants. Iron various fluids, ovarian endometriomas, follicles, ectopic lesions, peritoneal fluid. Markers strongly high levels, aberrant expression iron-transport proteins has demonstrated. Abnormal resistance ferroptosis likely. Iron-mediated responsible pro-inflammatory micro-environment and, possibly, transformation.A minority objectively low quality risk bias may lead misleading conclusions. Additionally, failed appropriately characterize patients known confounding variables, such as menstrual cycle phase, introduce findings.Current literature depicts central mechanics subsequent endometriosis. likely at least partly persistence proliferation lesions. As such, represent attractive target novel therapeutics, chelators effectors iron-oxidative pathway. There significant gaps current understanding, this highlights recommends several topics research. These include chelation, ferroptosis, relationship between localized hypoxia, systemic endometriosis, transformation.J.W. S.G.P. supported clinical fellowships Liverpool University Hospital NHS Foundation trust. No additional funding requested required completion work. C.J.H. Wellbeing Women project grant (RG2137). D.K.H. (RG2137) MRC research training fellowship (MR/V007238/1). authors conflicts interest declare.A protocol prospectively registered PROSPERO database 2021 (CRD42021272818).

Язык: Английский

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Immune Dysregulation in Endometriomas: Implications for Inflammation

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4802 - 4802

Опубликована: Апрель 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.

Язык: 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, Год журнала: 2024, Номер 5, С. 100061 - 100061

Опубликована: Янв. 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.

Язык: Английский

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The regulated cell death at the maternal-fetal interface: beneficial or detrimental?

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 26, 2024

Regulated cell death (RCD) plays a fundamental role in placental development and tissue homeostasis. Placental relies upon effective implantation invasion of the maternal decidua by trophoblast an immune tolerant environment maintained various cells at maternal-fetal interface. Although placenta can affect fetal even cause pregnancy-related diseases, accumulating evidence has revealed that several regulated were found interface under physiological or pathological conditions, exact types precise molecular mechanisms remain elusive. In this review, we summarized apoptosis, necroptosis autophagy play both promoting inhibiting roles differentiation, trophoblast, remodeling uterine spiral artery decidualization, whereas ferroptosis pyroptosis have adverse effects. RCD serves as mode communication between different to better maintain microenvironment. Maintaining balance is utmost importance for placenta, establishment microenvironment, prevention pregnancy disorders. addition, also association abnormal expression key molecules which may yield significant insights into pathogenesis treatment complications.

Язык: Английский

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Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Авг. 22, 2023

Abstract Endometriosis is strongly associated with infertility. Several mechanisms have been reported in an attempt to elucidate the pathophysiological effects that lead reduced fertility women endometriosis. However, by which endometriosis affects not fully elucidated. Ferroptosis a novel form of nonapoptotic cell death characterized iron-dependent lipid peroxidation membrane damage. In past reports, elevated iron levels ectopic lesions, peritoneal fluid and follicular patients The high-iron environment closely ferroptosis, appears exhibit double-edged effect on can cause damage ovarian granulosa cells, oocytes, embryos, leading endometriosis-related This article summarizes main pathways regulatory ferroptosis explores possible formation iron-overloaded endometriotic fluid. Finally, we reviewed recent studies potential

Язык: Английский

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