The role of maternal immune cells in early implantation sites has received special attention from reproductive biologists because immune cells participate in tissue transplant rejection. During normal pregnancy, endometrial immune cells differ from those in blood by subset distribution and appear to be activated but non-destructive of conceptuses. The immune system evolved well before placental mammals. By comparing the regulation and functions of endometrial immune cells between species in two phylogenetic clades that model differently evolved placental types (pig (Sus scrofa) versus mouse (Mus musculus) and human (Homo sapiens)), we seek to understand how ‘‘non-self’’ trophoblast cells
thrive in most pregnancies. Our studies suggest recruitment of specific immune cells to conceptusassociated endometrium and immune cell-promoted endometrial angiogenesis are of key importance for mammalian conceptus well-being.