Abstract
Background Recurrent spontaneous abortion (RSA) is commonly attributed to immune dysregulation at the maternal–fetal interface. The contribution of the spleen, as a peripheral immune organ, remains unclear. This study investigated spleen-associated immune alterations in a murine model of RSA. Methods An RSA model was established by mating CBA/J females with DBA/2 males. Splenic and decidual immune-cell distributions were assessed by histology, flow cytometry, and cytokine analysis. Splenectomy and macrophage depletion were performed as experimental interventions. Decidual transcriptomic changes following splenectomy were analyzed by bulk RNA sequencing and transcriptomic enrichment analyses. Results RSA mice exhibited splenomegaly, altered splenic histological features, and changes in splenic immune-cell composition, including increased numbers of Ly6C + CX3CR1 lo macrophages. Decidual immune alterations mirrored several changes observed in the spleen. Splenectomy was associated with increased embryo viability, reduced histological alterations, and changes in decidual immune-cell distributions. Similar effects on embryo viability and decidual immune-cell distributions were observed following effective macrophage depletion. Transcriptomic analyses of decidual tissue following splenectomy identified transcriptional differences involving mitochondrial-associated, Wnt-related, and protein synthesis-associated pathways. Conclusion These findings identify an association between spleen-associated immune alterations and RSA and suggest that splenectomy is accompanied by changes in decidual immune-cell distributions, tissue-level transcriptional patterns, and embryo viability.