We have found that progesterone signaling makes epithelial differentiation and stromal proliferation in the receptive uterus, which is involved in successful embryo implantation. We have also found that appropriate progesterone signaling with the proliferation/differentiation switching is disrupted in the cervix by microRNA-200a which directly reduces the expression of progesterone receptor and indirectly increases the expression of a progesterone-metabolizing enzyme 20α-HSD, indicating that the deficiency of progesterone signaling confers cervical non-responsiveness to embryo implantation. Moreover, we have found that uterine deletion of muscle segment homeobox genes induces aberrant inflammatory responses in the pre-receptive uterus as well as implantation failure with the altered uterine luminal epithelial cell polarity, suggesting the unique roles of Msx in uterine biology and embryo implantation.