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This study identifies the glutamine\/\u03b1-ketoglutarate (\u03b1-KG) metabolic axis as crucial for decidualization and demonstrates that \u03b1-KG supplementation can improve pregnancy outcomes, offering a potential therapeutic strategy for RIF.<\/jats:p>\n                  <jats:p>Abstract: Endometrial decidualization is a critical determinant of embryo implantation, and disruption in this process can lead to implantation failure. While various metabolic pathways regulate decidualization, the detailed metabolic characteristics and the mechanisms behind this remain unclear. Here we identified that during the process of decidualization, the concentrations of glutamine (Gln) and \u03b1-ketoglutarate (\u03b1-KG) were significantly elevated. Impaired Gln\/\u03b1-KG metabolism disrupts decidualization and triggers metabolic reprogramming characterized by decreased oxidative phosphorylation and glycolysis, leading to defective trophoblast spheroid adhesion and spreading. Further analysis revealed Gln\/\u03b1-KG metabolic abnormalities in the endometrial tissue of patients with recurrent implantation failure (RIF). Notably, supplementation with \u03b1-KG promotes decidualization and improves pregnancy outcomes (i.e., implantation number and pregnancy rate) in mice with impaired Gln\/\u03b1-KG metabolism. Thus, our study highlights the Gln\/\u03b1-KG metabolic axis as a key player in RIF, offering a scientific rationale for innovative preventive and therapeutic approaches.<\/jats:p>","DOI":"10.1093\/reprod\/xaag116","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:48:31Z","timestamp":1789040911000},"source":"Crossref","is-referenced-by-count":0,"title":["Altered glutamine\/\u03b1-ketoglutarate metabolism associates with decidualization defects in recurrent implantation failure and is ameliorated by \u03b1-ketoglutarate supplementation in mice"],"prefix":"10.1093","volume":"172","author":[{"given":"Zimeng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai,","place":["China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai,","place":["China"]},{"name":"Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Shi","sequence":"additional","affiliation":[{"name":"Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chinese University of Hong Kong , Hong Kong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shao","sequence":"additional","affiliation":[{"name":"Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine & Fertility Preservation Program, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chinese University of Hong Kong , Hong 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