Mucin and proteoglycan functions in embryo implantation.

Embryo implantation is a complex series of events that involves changes in pattern of expression of embryonic as well as uterine cell surface components. In the case of the embryo, these changes are driven by the developmental program. In the case of the uterus, these changes are triggered by both maternal hormonal influences as well as embryo-derived factors. Aspects of the implantation process vary among species; however, interaction between the external surface of the embryonic trophectoderm and the apical surface of the lumenal uterine epithelium is a common event. Progress is being made in defining the molecular players in these cell surface interactions. Large-molecular-weight mucin glycoproteins such as MUC1 are present at the apical surface of the uterine epithelium under most conditions. Under most circumstances, these mucins appear to protect the mucosal surface from infection and the action of degradative enzymes. These mucins are antiadhesive and also appear to represent a barrier to embryo attachment. Consistent with this model, reduction of mucin expression is observed in uterine lumenal epithelia in many species. Nonetheless, mucin expression persists in the human uterus during the proposed receptive phase. It is possible that mucin loss is localized to implantation sites in humans. Alternatively, mucins may function differently within the context of human implantation than in other species. Studies primarily performed in mice indicate that heparan sulfate proteoglycans, in particular, perlecan, appears on the exterior trophectodermal surface coincident with the acquisition of attachment competence. Various in vitro studies indicate that heparan sulfate proteoglycans support embryo attachment activity that may represent an early event in embryo-uterine interaction. Uterine epithelia cells express several complementary heparan sulfate-binding proteins that may participate in these attachment processes. Use of molecular genetic approaches in mouse models, as well as careful studies of the expression and function of these molecules in the context of implantation in various species are beginning to shed light on the key molecular events of implantation.