The metabolic landscape of the maternal-fetal interface in missed miscarriage: a cross-sectional pilot multiomics study

OBJECTIVE: To investigate the metabolic alterations at the maternal-fetal interface in missed miscarriage (MM) using untargeted metabolomic and lipidomic profiling of paired villous and decidual tissues. DESIGN: Observational study utilizing multiomics integration to analyze metabolic and lipidomic profiles. SUBJECTS: A total of 10 women were recruited in this study, including 5 women with MM and 5 healthy controls. All cases included in the MM group were euploid, excluding chromosomal abnormalities. EXPOSURE: The exposure in this study was the condition of MM, with tissue samples collected from both villous and decidual tissues. MAIN OUTCOME MEASURES: Differentially abundant metabolites and lipids between MM and control groups, focusing on metabolic pathways related to glycerophospholipid metabolism, sphingolipid signaling, and amino acid metabolism. RESULTS: We identified significant metabolic alterations in both villous and decidual tissues from MM pregnancies compared with healthy controls. Key findings included the downregulation of amino acids and organic acids, such as lactic acid, suggesting impaired energy metabolism. Lipidomic analysis revealed alterations in glycerophospholipids and sphingolipids, indicating disrupted cell signaling and inflammatory pathways in MM. CONCLUSION: This multiomics study highlights specific metabolic and lipidomic disruptions in MM, suggesting early metabolic disturbances at the maternal-fetal interface correlate with miscarriage. These findings may guide future therapeutic strategies targeting metabolic pathways to improve pregnancy outcomes in MM.