Adhesion molecules and implantation

Endometrial receptivity towards embryo implantation is a complex process that involves the ovary, endometrium and embryo. The dialog between the ovary and the endometrium provides the hormonal stimulus for establishment of a successful pregnancy. The hormones estrogen and progesterone act in concert to stimulate the expression of key molecules necessary for embryos to attach and invade. It is thought that initial attachment of the embryo involves cell adhesion events. The best characterized cell adhesion molecule on the luminal surface of the endometrium is the alphavbeta3 integrin. Its ligand osteopontin (OPN) is co-localized with alphavbeta3 and may play a role in endometrial or embryo signaling or facilitate embryo attachment to the apical surface prior to invasion. Surprising new evidence suggests that these two proteins are differentially regulated. Acting directly on endometrial epithelium, progesterone stimulates OPN expression. Using a stromal-mediated paracrine mechanism, HB-EGF or other EGF molecules appear to stimulate epithelial alphavbeta3 expression. In this article, we review what is known about these two pathways.