ArticleCell death & disease2022
Iron-overloaded follicular fluid increases the risk of endometriosis-related infertility by triggering granulosa cell ferroptosis and oocyte dysmaturity.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- The effects of antioxidant supplementation on pain, oxidative stress markers, and clinical pregnancy rate in women with endometriosis: a systematic review and meta-analysis of randomized controlled trials.Frontiers in medicine · 2025Pooled it
- NR4A1-Driven Granulosa Cell Ferroptosis Contributes to Obesity-Related Ovarian Dysfunction and Metformin-Mediated Ovarian Protection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Diagnostic and Predictive Values of Ferroptosis-Related Genes in Endometriosis Based on Integrated Bioinformatic Analysis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Icaritin improves pregnancy outcomes in endometriosis by inhibiting ovarian granulosa cell senescence.Molecular biology reports · 2026Article
- Do Oxidative Stress-Modified Exosomes Contribute to Infertility in Endometriosis?International journal of molecular sciences · 2026Review
- Ginsenoside Rb1 inhibits oxidative stress and ferroptosis to alleviate salpingitis infertility by down-regulating PTGS2 and up-regulating GPX4.Journal of ginseng research · 2026Article
- [Chronic iron overload induces diminished ovarian reserve in miceNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Immunomodulatory and antimicrobial actions of extracellular vesicles in vaginal infections: implications for female infertility.Molecular biology reports · 2026Review
- Revisiting the role of serum ferritin in PCOS: Beyond a singular biomarker perspective.Journal of Taibah University Medical Sciences · 2026Article
- The Microbiota-Endometriosis Axis: An Immune-Endocrine Integration Model and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Endometriosis disrupts oocyte metabolism and cortical granule function, impairing fertilization.Reproductive biology and endocrinology : RB&E · 2026Article
- Spermidine Targets Ovarian Granulosa Cells via Activating the FHC/SLC7A11 Axis to Regulate Iron Homeostasis and Ameliorate Iron Overload-Induced Ovarian Dysfunction.Antioxidants (Basel, Switzerland) · 2026Article
- HSD11B1 suppresses ferroptosis in endometrial stromal cells through the JUND/IL-10 axis to promote endometriosis progression.Reproductive biology and endocrinology : RB&E · 2026Article
- Article
- Relationship between different modes of death and premature ovarian insufficiency: a literature review.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactoferrin as a Non-Hormonal Therapeutic Candidate for Endometriosis: Mechanisms and Future Directions.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Variations in serum ferritin levels in women with polycystic ovarian syndrome undergoing assisted reproduction.Journal of Taibah University Medical Sciences · 2026Article
- Research Progress on Ferroptosis Regulation of Female Reproduction.Biological trace element research · 2026Review
- Zuogui Wan alleviated radiation-induced premature ovarian failure and ferroptosis via miR-21-5p/DNMT3b.Journal of ovarian research · 2026Article
- Feasibility study on QSM and R2* mapping for quantitative evaluation of iron deposition and ovarian function assessment in endometriotic ovarian cysts.La Radiologia medica · 2026Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endometriosis (EMs) occurs in approximately 50% of women with infertility. The main causes of EMs-related infertility are follicle dysplasia and reduced oocyte quality. Iron overload occurs in ovarian follicular fluid (FF) of patients with EMs, and this condition is associated with oocyte maturation disorder. However, the underlying molecular mechanism remains largely unknown. In the present study, we identified the mechanism underlying ferroptosis in ovarian granulosa cells and oocyte maturation failure in EMs based on a retrospective review of in vitro fertilization/intracytoplasmic sperm injection-frozen embryo transfer outcomes in infertile patients with EMs. Mouse granulosa cells were treated with EMs-related infertile patients' follicular fluid (EMFF) in vitro. Western blot analysis, quantitative polymerase chain reaction, fluorescence staining, and transmission electron microscopy were used to assess granulosa cells ferroptosis. The effects of exosomes were examined by nanoparticle tracking analysis, RNA-seq, and Western blot analysis. Finally, the therapeutic values of vitamin E and iron chelator (deferoxamine mesylate) in vivo were evaluated in an EMs-related infertility model. Patients with ovarian EMs experienced poorer oocyte fertility than patients with non-ovarian EMs. We observed that EMFF with iron overload-induced granulosa cell ferroptosis in vitro and in vivo. Mechanically, nuclear receptor coactivator four-dependent ferritinophagy was involved in this process. Notably, granulosa cells undergoing ferroptosis further suppressed oocyte maturation by releasing exosomes from granulosa cells. In therapeutic studies, vitamin E and iron chelators effectively alleviated EMs-related infertility models. Our study indicates a novel mechanism through which EMFF with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity in EMs-related infertility, providing a potential therapeutic strategy for EMs-related infertility.
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