ArticleCellular and molecular life sciences : CMLS2022
An active glutamine/α-ketoglutarate/HIF-1α axis prevents pregnancy loss by triggering decidual IGF1
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 19 citations in OpenAlex.
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Bidirectional Feedback Between Metabolic Reprogramming and Epithelial-Mesenchymal Transition: From Mechanisms to Therapeutic Interventions.Molecules (Basel, Switzerland) · 2026Review
- Decidual aging in recurrent pregnancy Loss: from regulating networks to therapeutic interventions.npj aging · 2026Review
- Integration of transcriptome and DNA methylation reveals the mechanism of cilia-related genes in recurrent miscarriage.Scientific reports · 2026Article
- Divergent Roles of HIF-1α and HIF-2α in Embryonic Development and Early Pregnancy.International journal of molecular sciences · 2026Review
- Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025Review
- Article
- Glutaminase activity maintains NK cell cytotoxicity through metabolic regulation of effector function.Journal of inflammation (London, England) · 2025Article
- Dual Role of Natural Killer Cells in Early Pregnancy: Immunopathological Implications and Therapeutic Potential in Recurrent Spontaneous Abortion and Recurrent Implantation Failure.Cell proliferation · 2025Review
- A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.Reproduction (Cambridge, England) · 2024Article
- Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies.Redox biology · 2024Review
- MiR-3074-5p Regulates Trophoblasts Function via EIF2S1/GDF15 Pathway in Recurrent Miscarriage.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
- Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction.Mediators of inflammation · 2024Article
- Recent insights into the role of hormones during development and their functional regulation.Frontiers in endocrinology · 2024Review
- Chenodeoxycholic Acid Improves Embryo Implantation and Metabolic Health through Modulating Gut Microbiota-Host Metabolites Interaction during Early Pregnancy.Antioxidants (Basel, Switzerland) · 2023Article
- Insufficient GDF15 expression predisposes women to unexplained recurrent pregnancy loss by impairing extravillous trophoblast invasion.Cell proliferation · 2023Article
- Consensus cluster analysis of apoptosis-related genes in patients with osteoarthritis and their correlation with immune cell infiltration.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion. Mechanistically, these processes are dependent on the downregulation of EGLN1-HIF-1α mediated by α-ketoglutarate (α-KG). Blocking glutaminolysis with the GLS inhibitor BPTES or the glutamate dehydrogenase inhibitor EGCG leads to early embryo implantation failure, spontaneous abortion and/or fetal growth restriction in pregnant mice with impaired trophoblast invasion. Additionally, α-KG supplementation significantly alleviated pregnancy loss mediated by defective glutaminolysis in vivo, suggesting that inactivated glutamine/α-ketoglutarate metabolism in dNK cells impaired trophoblast invasion and induced pregnancy loss.
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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.