Fetal sex dependent distribution of decidual immune cells at term

Specific pregnancy outcomes have been linked to fetal sex, with in general higher pregnancy complication rates in boy pregnancies. These pregnancy complications have been linked to dysregulated reactions of the maternal immune system. Previous studies show higher levels of pro-inflammatory cytokines in the decidua of boy pregnancies. It could therefore be that differences in pregnancy outcome are explained by fetal sex dependent maternal immune activation. This study aims to compare decidual immune cell subsets between girl and boy pregnancies with normal pregnancy outcomes. Lymphocytes and macrophages were isolated from fresh decidua basalis and parietalis and stained with CD4, CD8, CD69, CD103, CCR7, FOXP3, CD14, CD45, CD50, CD163 and HLA-DR and analyzed using flowcytometry. In addition, decidual tissue sections were stained for T cells (CD3), macrophages (CD68 and CD206) and NK cells (CD56) using immunohistochemistry. Statistical analysis was performed with unpaired T-test and Mann-Whitney U test. In total, 23 girl and 22 boy pregnancies were included. Using flowcytometry, levels of activated CD8+ T cells, CD8+ memory cells, central and tissue resident memory cells, and M1 macrophages were higher in the decidua basalis of boy pregnancies (p<0.05). In the decidua parietalis, M2-like macrophages were lower in boy pregnancies (p<0.05). The IHC cohort showed a relative higher number in FOXP3+ Treg cells (p< 0.05) in boy pregnancies. Higher numbers of activated T cells, memory cells and M1 macrophages in boy pregnancies could indicate more maternal immune activation in boy pregnancies. These findings could explain the higher complication rates in boy pregnancies.