Molecular Cues to Implantation

Abstract

Successful implantation is the result of reciprocal interactions between the implantation-competent blastocyst and receptive uterus.Although various cellular aspects and molecular pathways of this dialogue have been identified, a comprehensive understanding of the implantation process is still missing.The receptive state of the uterus, which lasts for a limited period, is defined as the time when the uterine environment is conducive to blastocyst acceptance and implantation.A better understanding of the molecular signals that regulate uterine receptivity and implantation competency of the blastocyst is of clinical relevance because unraveling the nature of these signals may lead to strategies to correct implantation failure and improve pregnancy rates.Gene expres-sion studies and genetically engineered mouse models have provided valuable clues to the implantation process with respect to specific growth factors, cytokines, lipid mediators, adhesion molecules, and transcription factors.However, a staggering amount of information from microarray experiments is also being generated at a rapid pace.If properly annotated and explored, this information will expand our knowledge regarding yet-to-be-identified unique, complementary, and/or redundant molecular pathways in implantation.It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.(Endocrine Reviews 25: 341-373, 2004) I. Introduction II.Preimplantation Embryo Development and Genomic Activation III.Species-Specific Morphological Blueprint and Timing of Implantation IV.Delayed Implantation V. Window of Implantation: A Transient and Unique Moment VI.Embryo-Uterine Signaling Pathways in Implantation A. Steroid hormone signaling B. Signaling via adhesion molecules: cell-cell interactions C. Signaling by vasoactive factors D. Signaling by growth factors E. Signaling by cytokines F. Homeobox genes in implantation G. Ligand-dependent nuclear receptors and coactivators in implantation H. Cell cycle regulation and signaling in implantation and decidualization I. Matrix remodeling and angiogenesis during implantation and decidualization VII.