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This study investigated metabolic reprogramming in RSA to identify diagnostic biomarkers. We integrated GEO datasets (GSE26787, GSE165004), identified metabolic reprogramming\u2010related differentially expressed genes, and intersected them with WGCNA modules. Module genes were refined using logistic regression, SVM\u2010RFE, and LASSO to construct a diagnostic model validated by ROC, nomogram, calibration, and decision curve analysis. The role of\n                    <jats:italic>SREBF2<\/jats:italic>\n                    was explored by PCR, western blot, CCK\u20108, and transwell assays in vitro. Immune infiltration (ssGSEA, CIBERSORT) and single\u2010cell RNA sequencing (GSE214607) explored immune\u2010metabolic crosstalk. Results demonstrate critical involvement of metabolic reprogramming in RSA. Four model genes (\n                    <jats:italic>SREBF2<\/jats:italic>\n                    ,\n                    <jats:italic>PPARG<\/jats:italic>\n                    ,\n                    <jats:italic>SQLE<\/jats:italic>\n                    ,\n                    <jats:italic>UCP2<\/jats:italic>\n                    ) were upregulated in RSA and enriched in lipid\/cholesterol pathways. Experimental validation confirmed\n                    <jats:italic>SREBF2<\/jats:italic>\n                    upregulation in RSA decidua. Its overexpression in endometrial stromal cells impaired cell proliferation, decidualization, and trophoblast migration. Immune infiltration revealed correlations between model genes and specific immune subsets. Single\u2010cell analysis identified altered immune cell proportions and cell\u2010type\u2010specific expression patterns, predominantly in macrophage subsets. This study indicates that lipid\u2010centric metabolic remodelling may concurrently affect decidual function, trophoblast behaviour, and immune tolerance in RSA, offering diagnostic and therapeutic insights.\n                  <\/jats:p>","DOI":"10.1049\/syb2.70078","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:54:56Z","timestamp":1781740496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Reprogramming in Recurrent Spontaneous Abortion: Key Biomarkers Identification and Diagnostic Model Development"],"prefix":"10.1049","volume":"20","author":[{"given":"Fan","family":"Wu","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 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