Deconvoluting the heterogeneities of immune cells at the maternal‒fetal interface of mice across pregnancy

Homeostasis of immune microenvironment at the maternal–fetal interface is essential for pregnancy. Immune cell heterogeneity at the maternal–fetal interface in pregnant mice remains understudied. Here, we perform in-depth single-cell transcriptomic analysis with 120,238 maternal–fetal single cells of mice from embryonic day 7.5 (E7.5) to E18.5 and in vitro experiments to establish an immune cell atlas. Macrophages constitute the largest population, with some subsets resembling human counterparts, and the number of Ccr2 + macrophages in the decidua increases as pregnancy progresses. Neutrophils constitute the second largest population, and Ifit1 + N2 neutrophils are localized close to the implantation site during early pregnancy. Three NK cell subsets were identified, including the previously reported NK1.1 - subset. In combination with in vitro experiments, the presence of T and B cells within the decidua was validated. Our work profiles a comprehensive immune cell atlas of the mouse maternal–fetal interface, offering a valuable reference for further investigations. In brief Mice often serve as valuable surrogate models for studying human reproduction. This study provides a single-cell transcriptomic profile of mouse immune cells at the maternal‒fetal interface throughout pregnancy and assesses the similarities and differences between these immune cells and human decidual immune cells.