Possible mechanisms to create an adequate period of cross-talk between the embryo and mother before attachment by repulsive forces. (A) During human embryo implantation, several adhesion-promoting molecules, such as trophinin, L-selectin ligand, and integrin αVβIII, are expressed on endometrial epithelial cells during the receptive phase. In contrast, large glycoproteins, such as MUC1, that inhibit the physiological cell-to-cell interaction are expressed on the murine and human luminal epithelial layer. (B) During the implantation window, the expression of adhesion-promoting molecules increases, whereas that of adhesion-inhibiting molecules decreases in cooperation with embryonic signals, leading to cell-to-cell interaction between the embryo and endometrial epithelial cells. This enables the embryo to receive Eph signals from endometrial epithelial cells through ephrin ligands on its surface, leading to repulsive forces between the embryo and endometrium. (C–E) By repulsive forces through the Eph–ephrin system, the embryo separates from the endometrium (white two-way arrow), repeating attachment and detachment. (F) Finally, the embryo attaches to appropriate sites with suitable timing.