Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 30, 2024

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal tissue structure reduced strength in patients with diabetes. Studies have revealed close association among diabetes, increased fracture risk, disturbances iron metabolism. This review explores concept of ferroptosis, non-apoptotic cell death process dependent on intracellular iron, focusing its role DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic β-cells, osteoblasts (OBs) osteoclasts (OCs), contributes to The intricate interplay between dysregulation, which comprises deficiency overload, DOP has been discussed, emphasizing how excessive accumulation triggers ferroptosis concise overview highlights need understand complex relationship T2DM OP, ferroptosis. aimed elucidate pathogenesis provide prospective for future research targeting interventions field

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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Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Дек. 13, 2023

The ovarian microenvironment is critical for follicular development and oocyte maturation. Maternal conditions, including polycystic ovary syndrome (PCOS), endometriosis, aging, may compromise the microenvironment, development, quality. Chronic low-grade inflammation can induce oxidative stress tissue fibrosis in ovary. In PCOS, pro-inflammatory cytokine levels are often elevated fluids. women with obesity hyperandrogenemia insulin resistance chronic inflammation, thereby disrupting by increasing stress. endometrioma-derived iron overload stress, leading to ferroptosis fibrosis. inflammatory aging (inflammaging), senescent cells secrete senescence-associated secretory phenotype factors, causing Therefore, controlling would present a novel therapeutic strategy improving minimizing dysfunction.

Язык: Английский

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Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS

Human Reproduction Open, Год журнала: 2024, Номер 2024(2)

Опубликована: Янв. 1, 2024

Abstract STUDY QUESTION Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Increased was present PCOS ovaries and inhibition with ferrostatin-1 (Fer-1) ameliorated morphology anovulation. WHAT IS KNOWN ALREADY Programmed cell death plays a fundamental follicle development. However, types mechanisms involved are yet to be elucidated. Ferroptosis is recently discovered iron-dependent programmed death. Impaired iron metabolism have been observed women PCOS, main cause anovulatory infertility. Additionally, previous studies reported that abnormal expression noncoding RNA may promote immortalized granulosa lines. little known about whether increased there insufficient direct evidence for underlying mechanism. Moreover, effect Fer-1 remains unclear. DESIGN, SIZE, DURATION evaluated human cells (hGCs) from non-PCOS (n = 6–16) 7–18) patients. The experimental study completed vitro using primary hGCs undergoing IVF. Improvements indicators following were investigated dehydroepiandrosterone (DHEA)-induced rat model 8 per group). PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian ways: by detecting concentrations via ELISA fluorescent probes; measuring malondialdehyde (MDA) ELISA; assessing ferroptosis-related protein abundance western blotting; observing mitochondrial transmission electron microscopy; determining viability. Primary collected They treated dihydrotestosterone (DHT) 24 h. DHT on examined presence or absence small interfering RNA-mediated knockdown putative receptor coregulator signaling molecules. progression explored vivo rats. DHEA-induced inhibitor, Fer-1, oocytes metaphase II counted after stimulation. rats inducer, RSL3, further explore ferroptosis. testosterone, FSH, LH assessed. MAIN RESULTS AND THE ROLE OF CHANCE detected patients PCOS. Fe2+ (P < 0.05) MDA 0.05), upregulated nuclear coactivator 4 levels, downregulated ferritin heavy chain 1 (FTH1) glutathione peroxidase (GPX4) proteins 0.05 versus control). shown induce activation NOCA4-dependent ferritinophagy. cluster traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, ovaries, anovulation, oocyte quality 0.05). Treating RSL3 resulted hyperandrogenism LARGE-SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Although ovarian-targeted more targeted treatment cycle between require exploration. since shows high heterogeneity, it important investigate increases all WIDER IMPLICATIONS FINDINGS Androgen-induced appears pathogenesis which potentially makes promising target FUNDING/COMPETING INTEREST(S) This supported National Key R&D Program China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), Natural Science Foundation (No. 82130046, 82320108009, 82101708, 82101747, 82001517), Shanghai leading talent program, Innovative research team high-level local universities SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Jiaotong University School Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund (RJPY-DZX-003) Municipal Education Commission—Gaofeng Medicine Grant Support 20161413), Shanghai’s Top Priority Center Construction Project (2023ZZ02002), Three-Year Action Plan Strengthening Public Health System (GWVI-11.1-36). authors report no competing interests.

Язык: Английский

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Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(9)

Опубликована: Апрель 17, 2024

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes heavy economic burden on people and society. Although it well established IVDD associated with genetic susceptibility, ageing obesity, its pathogenesis remains incompletely understood. Previously, was thought to occur because of excessive mechanical loading leading destruction nucleus pulposus cells (NPCs), but studies have shown much more complex process inflammation, metabolic factors NPCs death can involve all parts the disc, characterized by causing extracellular matrix (ECM) degradation. The damage pattern like some programmed cell death, suggesting death. apoptosis pyroptosis been studied IVDD, intervertebral still not be fully elucidated using only traditional modalities. With increasing research, new modes PANoptosis, ferroptosis senescence found closely related degeneration. Among these, PANoptosis combines essential elements pyroptosis, necroptosis form highly coordinated dynamically balanced inflammatory process. Furthermore, we believe may also crosstalk senescence. Therefore, review progress research multiple deaths provide guidance for clinical treatment.

Язык: Английский

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Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health

Nutrients, Год журнала: 2024, Номер 16(7), С. 1008 - 1008

Опубликована: Март 29, 2024

The role of minerals in female fertility, particularly relation to the menstrual cycle, presents a complex area study that underscores interplay between nutrition and reproductive health. This narrative review aims elucidate impacts on key aspects system: hormonal regulation, ovarian function ovulation, endometrial health, oxidative stress. Despite attention given specific micronutrients disorders, there is noticeable absence comprehensive focusing impact throughout cycle fertility. address this gap by examining influence Each mineral’s contribution explored detail provide clearer picture its importance supporting analysis not only enhances our knowledge health but also offers clinicians valuable insights into potential therapeutic strategies recommended intake promote well-being, considering cycle. stands as first offer such detailed examination context aiming elevate understanding their critical fertility

Язык: Английский

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Ovarian Endometrioma Disrupts Oocyte‐Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects

Cell Proliferation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

ABSTRACT Ovarian endometrioma (OEM), a particularly severe form of endometriosis, is an oestrogen‐dependent condition often associated with pain and infertility. The mechanisms by which OEM impairs fertility, through its direct impact on oocyte‐cumulus cell (CC) communication related pathways, remain poorly understood. This study investigates the oocyte‐CC explores melatonin's therapeutic potential. We used mouse model employed ovarian transcriptome gene set enrichment analyses to identify disrupted alongside phalloidin staining for cytoskeletal analysis, gap junction coupling analysis intercellular communication, mitochondrial function assessments cellular metabolism. Our results showed that significantly steroidogenesis cumulus function, leading increased apoptosis, transzonal projections (TZPs), impaired antioxidant transfer oocytes. culminates in oxidative stress, dysfunction, compromised ATP production. oocytes also exhibited abnormalities, including DNA damage, maturation defects, spindle assembly disruptions, aneuploidy. identifies TZPs as key pathological feature highlights potential restore mitigate improve reproductive outcomes.

Язык: Английский

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

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 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

Язык: Английский

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Ferroptosis and musculoskeletal diseases: “Iron Maiden” cell death may be a promising therapeutic target

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 11, 2022

Ferroptosis is a novel form of cell death precisely regulated by iron metabolism, antioxidant processes, and lipid metabolism that plays an irreplaceable role in the development many diseases. Musculoskeletal disorders (MSKs), including osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, sarcopenia, rhabdomyolysis, have become one most common causes disability major burden on public health social care systems. The mechanism ferroptosis MSKs has recently been elucidated. In this review, we briefly introduce illustrate pathological roles with focus how can be exploited as promising treatment strategy. Notably, because toxicity compounds inhibit or induce other organs largely unknown, appears to double-edged sword. We point out more research needed future verify therapeutic effects based MSKs.

Язык: Английский

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Expecting more: the case for incorporating fertility services into comprehensive sickle cell disease care

The Lancet Haematology, Год журнала: 2023, Номер 10(3), С. e225 - e234

Опубликована: Янв. 26, 2023

Язык: Английский

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