ABSTRACT
The success of implantation process depends on a synchronous and reciprocal complex molecular interaction between the embryo and the hormonally primed maternal endometrium, which occurs approximately 6 or 7 days after fertilization during a restricted window of receptivity lasting 4 or 5 days. This process requires carefully orchestrated interactions between cells and their extracellular matrix environment mediated by numerous factors and the challenge of the maternal immune system by paternal antigens. Various immune cells and molecules present in the endometrium during the window of implantation not only are involved in the control of trophoblast invasion and the maternal response to fetal allograft but also modulate the vascular remodeling during placental development. The maternal immune response is shifted toward humoral im munity and away from cell-mediated immunity that could be harmful to the fetus, and the progesterone produced by the corpus luteum stimulates an anti-inflammatory response, which decreases the secretion of proinflammatory cytokines and suppresses allogeneic response, allowing fetal survival. Human embryo implantation is a three-stage process including apposition, adhesion, and invasion. During apposition, the trophoblast becomes closely apposed to the luminal endometrial epithelium and the pinopodes, and micro protrusions involved in endocytosis and pinocytosis found on the apical surface of endometrial epithelium during the window of receptivity interdigitate with microvilli on the apical syncytiotrophoblast surface of the blastocyst facilitating its adhesion to the luminal epithelium. The adhesion stage is characterized by the attachment of apical plasma membranes of the trophectoderm (TE) and endometrial epithelial cells over which a mucin containing glycocalyx is present and represents a barrier to trophoblast invasiveness. During this stage, the blastocyst triggers the local loss of the repelling mucin 1 favoring the communication between TE and endometrial epithelial cells, and several chemokines secreted locally either by the embryo or by the endometrium during the implantation window act as signals for receptor polarization and activation of endometrial adhesion molecules. Following adhesion, the blastocyst invades through the luminal epithelium into the stroma up the uterine vessels using different matrix metalloproteinases involved in the proteolysis of the extracellular matrix. Under maternal control, endometrial decidualization is fundamental for placental formation, including the regulation of trophoblast invasion, to modulate local vascular/immune responses and to resist environmental and oxidative stress, all of which contribute to the viability of the pregnancy. The implantation period of development represents a critical time during which the interactions between the embryo and the maternal endometrium are highly susceptible to exogenous insults that can affect future growth and developmental potential, either prenatally or postnatally. Environmental contaminants such as endocrine disruptors may cause an imbalance of ovarian steroid hormone production, which negatively affects uterine receptivity, and exposure to toxicants may result in the disruption of maternal immune response, which compromises the placentation process and pregnancy development. This chapter reviews current knowledge
about key molecular, cellular, immunological, and endocrine events involved in maternal recognition of pregnancy. The effects of the exposure to reproductive toxicants on the window of implantation and on the embryo-endometrial communication are briefly discussed.
