Molecular Interactions at the Maternal-Embryonic Interface
In mammals the embryo must implant in the uterus and develop a placenta to gain nutrition and facilitate gas exchange. In this article, the earliest events in this process are reviewed. The embryo can implant only when it has reached the blastocyst stage. The blastocyst is composed of an inner clump of cells, the inner cell mass, that gives rise to the fetus and an outer layer of trophectoderm (TE), the precursor of the placenta. Both blastocyst and uterus must differentiate in parallel to reach the appropriate state of maturity (activated blastocyst and receptive uterus) at which implantation can occur. Interaction between TE and the luminal epithelium (LE) lining the uterus initiates implantation, and both soluble signals and association between molecules on apposed surfaces appear to be involved. A number of cell surface molecules have been implicated in the initial attachment between TE and LE. These include HSPG, Le-y and the H-type-1 antigen, HB-EGF, trophinin-tastin-bystin complex, integrins, and extracellular matrix molecules such as osteopontin and laminin. Others, such as mucins, may need to be removed or modified to allow adhesion to proceed. Evidence for the role of these components is discussed.

Reproduction in mammals is characterized by fertilization and early embryonic development within the female reproductive tract, after which the conceptus implants in the wall of the uterus. This allows development of the placenta to supply the fetus with nutrients and oxygen and remove waste products. In spite of the variation between species in the detailed events of embryo implantation, there is considerable similarity, as for other developmental processes. Control of uterine differentiation by ovarian steroids is a common factor, although molecular details differ. Implantation requires a common attachment phase in which the outer layer of the blastocyst, the trophectoderm (TE), interacts with the lining epithelium (LE) of the uterus. Both human implantation and murine implantation involve invasion of maternal tissues by trophoblast cells, although the extent of this invasion differs. The size and complexity of the mouse and human placentae are considerably different, as reflected in the length of time the placenta is needed to support the fetus (19-20 days gestation in the mouse and 38 weeks in human). However, similarities in cell biology and architecture are also being recognized. The erosion of maternal cell layers occurs in parallel in the formation of murine and human hemochorial placentae.

We know little about the initial events of implantation in humans because even rare histological specimens are too late to be very informative. Intimate contact with the uterine wall takes place over a short period in the luteal phase of the menstrual cycle. Ethical considerations prevent observation, so much of our knowledge of how the embryo develops from a blastocyst in the uterine lumen to a firmly embedded conceptus within the uterine wall comes from animal models. A few studies have been carried out on human blastocyst attachment in vitro. In addition, evidence for molecular expression by human blastocysts (including cell adhesion molecules) is accumulating. This may help us to predict whether factors implicated in implantation from experiments in other species could also be involved in humans.