The time course of events leading to embryo implantation in the mouse. (a) On day 3 after fertilization the uterus is undergoing differentiation and proliferation under control of the ovarian steroid hormones estrogen and progesterone. (b) On day 4 the blastocyst is adjacent to the uterus and the production of leukemia inhibitory factor (LIF) is induced in the endometrial glands by nidatory estrogen. LIF is released into the uterine lumen, where it binds to LIF receptors on the luminal epithelium. LIF binding induces the expression of many genes, including the cell adhesion factors Coch and CD9, as the uterus becomes receptive to the embryo allowing the onset of implantation. Other adhesion molecules, such as E-cadherin, undergo redistribution in their expression. (c) On day 5 the blastocyst has started to invade the uterus and the stroma is undergoing decidualization, accompanied by the expression of prostaglandins (PGEs), which are regulated by Cox-2, and the cytokine interleukin-11 (IL-11), which is essential for decidualization.