ArticleProceedings of the National Academy of Sciences of the United States of America2020
PLA2G6 guards placental trophoblasts against ferroptotic injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
What it found
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The trial behind it
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Who cites it
107 citing papers in PubMed, 179 citations in OpenAlex.
- Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026Review
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- Metabolic Reprogramming at the Maternal-Fetal Interface: Insights from Decidual Stromal Cells and Trophoblasts in Healthy Pregnancy Versus Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Review
- Decidual macrophage-mediated ferroptosis in trophoblasts leads to recurrent spontaneous abortion.iMeta · 2026Article
- Research Progress on the Role of Traditional Chinese Medicine in Regulating Ferroptosis in Cardiovascular Diseases.Biology · 2026Review
- Placental ferroptosis and impaired fetal growth in symptomatic and asymptomatic SARS-CoV-2 infections.Clinical science (London, England : 1979) · 2026Article
- Research Progress on Ferroptosis Regulation of Female Reproduction.Biological trace element research · 2026Review
- Polystyrene Nanoparticles Disrupt Oxidative Phosphorylation and Impair Placental Development in Mice.Toxics · 2026Article
- Trophoblast ferroptosis restricts SARS-CoV-2 spread in the placenta.bioRxiv : the preprint server for biology · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Context-dependent Activities of Mitrephorone Link Lipid Redirection, Anti-inflammatory Action, and Ferroptosis Control to Hepatocyte Protection.Theranostics · 2026Article
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Lipid remodeling and ferroptosis in phosphatidylcholine-mediated tumor-stroma crosstalk.Frontiers in molecular biosciences · 2026Review
- Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025Review
- Oxidative stress, mitochondrial dysfunction, and ferroptosis in the placenta of gestational diabetes mellitus.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Deficiency of PLA2G6 Induces Ferroptosis in Dopaminergic Neurons and Contributes to Parkinson's Disease Pathogenesis via Disruption of PRDX6/FTH1/GPX4 Axis.Molecular neurobiology · 2025Article
- Macrophages rescue cells from ferroptotic death.Cell death & disease · 2025Article
- Influenza a(H1N1) virus infection impairs syncytiotrophoblast functions by promoting ferroptosis through the TNF-α/ISG15/EGR1 axis.Virology journal · 2025Article
- Iron and selenium: At the crossroads of development and death in oligodendrocytes.Archives of biochemistry and biophysics · 2025Review
- The Emerging Roles of Ferroptosis and NETosis in Pregnancy Complications: Insights into Preeclampsia and Gestational Diabetes Mellitus.Current issues in molecular biology · 2025Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The recently identified ferroptotic cell death is characterized by excessive accumulation of hydroperoxy-arachidonoyl (C20:4)- or adrenoyl (C22:4)- phosphatidylethanolamine (Hp-PE). The selenium-dependent glutathione peroxidase 4 (GPX4) inhibits ferroptosis, converting unstable ferroptotic lipid hydroperoxides to nontoxic lipid alcohols in a tissue-specific manner. While placental oxidative stress and lipotoxicity are hallmarks of placental dysfunction, the possible role of ferroptosis in placental dysfunction is largely unknown. We found that spontaneous preterm birth is associated with ferroptosis and that inhibition of GPX4 causes ferroptotic injury in primary human trophoblasts and during mouse pregnancy. Importantly, we uncovered a role for the phospholipase PLA2G6 (PNPLA9, iPLA2beta), known to metabolize Hp-PE to lyso-PE and oxidized fatty acid, in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia/reoxygenation injury in vivo. Together, we identified ferroptosis signaling in the human and mouse placenta, established a role for PLA2G6 in attenuating trophoblastic ferroptosis, and provided mechanistic insights into the ill-defined placental lipotoxicity that may inspire PLA2G6-targeted therapeutic strategies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.