Metabolic reprogramming of decidual macrophages impairs maternal-fetal interface homeostasis and contributes to recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is a troublesome pregnancy disorder, and metabolic reprogramming of decidual macrophages is implicated in disrupted maternal-fetal interface homeostasis and RSA pathogenesis, yet the specific mechanism remains poorly defined. This study aimed to explore the regulatory role of GTP-binding protein 10 (GTPBP10) in RSA by targeting macrophage metabolic reprogramming. We detected GTPBP10 expression in decidual macrophages from RSA patients and healthy controls, and investigated its effects on macrophage phenotypes, glycolysis and fatty acid oxidation (FAO) via gene overexpression/knockdown, metabolic detection, and multiple molecular experiments. The direct interaction between GTPBP10 and AMPK was verified, and in vivo mouse models and cell co-culture systems were constructed for functional validation. Results showed that GTPBP10 was markedly upregulated in RSA-derived decidual macrophages and induced a pro-inflammatory macrophage phenotype. Mechanistically, GTPBP10 bound and inhibited AMPK phosphorylation, promoting glycolysis while suppressing FAO and causing mitochondrial damage; these aberrations were rescued by the AMPK activator AICAR. In vivo, GTPBP10-overexpressing macrophages increased embryo resorption, impaired placental vasculature and triggered pro-inflammatory immune imbalance. Moreover, macrophage GTPBP10 overexpression inhibited trophoblast motility, impaired endometrial decidualization and biased CD4+ T cells toward Th1/Th17 phenotypes. In conclusion, GTPBP10-mediated AMPK inhibition triggers immunometabolic reprogramming of decidual macrophages, disrupts maternal-fetal immune homeostasis, and ultimately drives the occurrence of RSA, providing a promising therapeutic target for RSA.