Metabolic Reprogramming at the Maternal–Fetal Interface: Insights from Decidual Stromal Cells and Trophoblasts in Healthy Pregnancy Versus Recurrent Pregnancy Loss

Metabolic reprogramming at the maternal–fetal interface remodels enzymes, metabolites, and pathways to orchestrate decidualization, placentation, and immune tolerance, thereby sustaining cellular homeostasis and maternal-fetal adaptation. Disruption of this precisely coordinated metabolic reprogramming impairs these processes, contributing to recurrent pregnancy loss (RPL). This review focuses on the two most abundant cell types at the maternal–fetal interface: maternal-derived decidual stromal cells (DSCs) and embryo-derived trophoblasts, and systematically delineates their metabolic reprogramming in healthy pregnancy versus RPL. Recent advances reveal that altered glucose, lipid, amino acid, redox, and one-carbon metabolism in DSCs and trophoblasts drives defective decidualization, placentation, and immune tolerance, offering novel mechanistic insights into RPL etiology. These findings highlight potential metabolic biomarkers and therapeutic strategies, bridging mechanistic discoveries with translational opportunities for RPL.