ArticleCell reports. Medicine2023
Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 20 citations in OpenAlex.
- Microbial and Metabolic Correlates of Endometrial Dysfunction in Polycystic Ovary Syndrome: A Translational Study.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- ALKBH5 Positively Regulates BMP2 to Influence Endometrial Decidualization in Recurrent Spontaneous Abortion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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
- Downregulation of fibroblast growth factor 7 impairs endometrial receptivity and decidualisation via extracellular signal-regulated kinase and C-Jun N-Terminal kinase pathways, contributing to recurrent spontaneous abortion.Journal of molecular histology · 2026Article
- Decidual aging in recurrent pregnancy Loss: from regulating networks to therapeutic interventions.npj aging · 2026Review
- HBP1 enhances progesterone receptor activity and IGFBP1 expression driving endometrial decidualization.Communications biology · 2026Article
- METTL3 safeguards cell identity and epigenome of human trophoblast stem cells.Nature communications · 2025Article
- Article
- Exploring the epigenetic mechanisms of recurrent pregnancy loss: from genetic predisposition to environmental influences.Journal of assisted reproduction and genetics · 2025Review
- Regulatory Interplay of p53, AMPK, and mTOR in Decidualization: Implications for Reproductive Competence and Cancer Biology.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Amino Acid Restriction Impairs Human Endometrial Stromal Cell Decidualization and Is Rescued by Proline Supplementation.Journal of cellular and molecular medicine · 2025Article
- Obesity and recurrent spontaneous abortion: the crucial role of weight management in pregnancy.Reproductive biology and endocrinology : RB&E · 2025Review
- Angelica sinensis polysaccharide as potential protectants against recurrent spontaneous abortion: focus on autophagy regulation.Frontiers in medicine · 2025Article
- Glucose metabolism and endometrium decidualization.Frontiers in endocrinology · 2025Review
- A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.Reproduction (Cambridge, England) · 2024Article
- TNFSF14The EMBO journal · 2024Article
- Unveiling the atlas of associations between 1,400 plasma metabolites and 24 tumors: Mendelian randomization analyses.Translational cancer research · 2024Article
- Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- [Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.
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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.