(A) The expression of HAND2 (large red circles) was measured at the maternal-fetal interface across multiple placental and non-placental species. Marinić et al. then used ancestral reconstruction to infer that the expression of HAND2 (small red circles) at the maternal-fetal interface arose in the ancestor of all placental mammals (shown in purple). In the wallaby, the expression of HAND2 has a distinct evolutionary origin, which is most likely associated with other derived pregnancy traits in this species. (B) The placenta (fetal; purple) and uterine wall (maternal; gray) meet at the maternal-fetal interface, where nutrients and waste are exchanged, and communication systems are established. (C) During early pregnancy, HAND2 is highly expressed at the maternal-fetal interface: the resulting increase in IL15 expression leads to immune natural killer cells (NK cells) being recruited to the interface (top), where they help to shape the structure. As pregnancy progresses, decreased HAND2 and IL15 expression alters the recruitment of NK cells, which may have a role in determining when birth should start.