ABSTRACTProblemDuring pregnancy, the maternal immune system undergoes different adaptations to establish tolerance toward the fetus. Several factors are known to affect maternal immune adaptations, including fetal allo‐antigens. Although, the effects of fetal antigens have clearly been shown in early pregnancy, the influence of these antigens in mid‐ and late pregnancy are not fully known.Method of StudyIn this study, we investigated the impact of fetal allo‐antigens during pregnancy on maternal immune adaptations by comparing immunological changes in semi‐allogeneic and syngeneic pregnancies in mice. Pregnant mice were analyzed at gestation day 10 (GD10) and gestation day 18 (GD18), and immune responses were assessed in the spleen, uterus draining para‐aortic lymph nodes (PALN) and peripheral blood analyzing T cells, monocytes and their subsets. In addition, T cells were analyzed after stimulation using PMA or male antigens.ResultsAnalyses of memory T cells, Tregs and monocytes (and subsets) demonstrated that fetal semi‐allogeneity only had a minor influence on the maternal immune parameters in mid and late gestation. Immune stimulation experiments, using either PMA or syngeneic or allogeneic paternal antigens, revealed minor differences in cytokine production between general immune stimulation and paternal specific stimulation.ConclusionsOur results show that immune adaptations ad mid and late pregnancy are likely not mainly driven by fetal allo‐antigens. This study contributes to a deeper understanding of the maternal immune system during pregnancy (either syngeneic or semi‐allogeneic).