A lesson learned from modern developmental biology is the striking degree of conservation of strategies and molecules used to program developmental events in species as diverse as insects, birds, amphibians, and mammals. Nonetheless, mammals retain distinctions with regard to the strategies used to protect and nourish their offspring during development, namely the processes of implantation and placentation. While involving relatively few cell types, placentation is a complex process. Furthermore, genes associated with this process display remarkably high spontaneous mutational rates, suggesting a strong adaptive/selection pressure on this tissue (Roberts et al., 1999). In the case of implantation, a highly coordinated process is set into motion whereby specialized cells of the embryo, the trophectoderm and trophoblast, establish contact with a specialized tissue of the mother, the uterus. The exquisite coordination involves the regulated production of growth factors, cytokines, and hormones by embryonic as well as maternal tissues of both uterine and extrauterine origins. In concert, complementary receptors for these factors must be expressed by the appropriate tissues to propagate implantation signals. In addition, cell surface components must become functionally available to support attachment of trophectoderm/trophoblast and uterine cells. To add to the challenge, it has been shown that, in most mammals, there is only a restricted time during the uterine cycle during which implantation can occur (Psychoyos, 1986). Failure to initiate the critical early events of implantation during this “window of receptivity” results in early pregnancy failure. In addition to processes occurring in the embryo during the pre-and peri-implantation period, uterine events also may be considered in a developmental context. The uterus undergoes dynamic changes during the cycle and displays many features typical of developmental processes, including differential and ordered activation or repression of gene expression and programmed changes in posttranscriptional and posttranslational modifications of mRNA and proteins. While the progression of these events is largely driven by endocrine actions, they display the same sequential nature as classical developmental processes. In the absence of an embryo, the uterus will progress through a predictable series of stages ultimately terminating in tissue regression and apoptosis. In the presence of an embryo, the endometrium not only is maintained, but also progresses through an additional program of events, ie, the decidual cell response, leading to prolonged maintenance and additional programs of gene expression that otherwise are not observed (Parr and Parr, 1989). Thus, multipotentiality is displayed by uterine tissue.

From the above, it is apparent that, even though embryonic development may proceed normally, there remain many opportunities for implantation failure. In this regard, while marked improvements in in vitro fertilization and embryo culture techniques have been made over the past 20 years, pregnancy success rates following these procedures have improved only marginally (ASRM Report, 1999). This has led to the proposition that additional uterine factors, critical for the implantation process, must be limiting. Identification of such parameters could lead to tests used in conjunction with available serum and histological assays to