Splenic ectopic pregnancy is a rare and life-threatening condition, with no prior studies exploring its immune microenvironment. We analyzed immune cell alterations in splenic ectopic pregnancy and the potential role of macrophages in pregnancy using immunohistochemical staining, transcriptomic profiling, and histological analysis. Our findings suggest that M2 macrophages may play a crucial role in maintaining successful pregnancy. The biological effects of macrophages on trophoblast cells were evaluated through CCK-8, migration, and invasion assays. Our results demonstrated that in splenic ectopic pregnancy tissues, significant reductions in CD20 + B cells, CD8 + T cells, and CD86 + M1 macrophages were observed within splenic regions, while CD206 + M2 macrophages were markedly increased in areas of trophoblast cell infiltration. This predominance of M2 macrophages may promote embryonic survival in splenic ectopic implantation. Transcriptomic and histological analyses of endometrial tissues from recurrent miscarriage (RM) patients revealed comparable M1/M2 macrophage dysregulation. In vitro experiments further demonstrated that M2 macrophages significantly enhanced trophoblast cell migration and invasion via PDGFR-β and PI3K-AKT-mTOR pathway. This study is the first to analyze the immune microenvironment of splenic ectopic pregnancy, revealing the critical role of M2 macrophages in maintaining normal immune tolerance. • Analysis of immune microenvironment in splenic ectopic pregnancy shows rise in CD206 + M2 macrophages in trophoblast regions. • Endometrial tissues from patients with recurrent miscarriage also exhibit M1/M2 macrophage imbalance. • M2 macrophages boost trophoblast migration and invasion, implying a vital role in sustaining successful pregnancy.
Li et al. (2026) studied this question.