Global gene expression analysis to identify molecular markers of uterine receptivity and embryo implantation

Infertility and spontaneous pregnancy losses are an enduring problem to wom en's health. The establishment of pregnancy depends on successful implantat ion, where a complex series of interactions occurs between the heterogeneou s cell types of the uterus and blastocyst. Although a number of genes are i mplicated in embryo-uterine interactions during implantation, genetic evide nce suggests that only a small number of them are critical to this process. To obtain a global view and identify novel pathways of implantation, we us ed a dual screening strategy to analyze the expression of nearly 10,000 mou se genes by microarray analysis. Comparison of implantation and interimplan tation sites by a conservative statistical approach revealed 36 up-regulate d genes and 27 down-regulated genes at the implantation site. We also compa red the uterine gene expression profile of progesterone-treated, delayed im planting mice to that of mice in which delayed implantation was terminated by estrogen. The results show up-regulation of 128 genes and down-regulatio n of 101 genes after termination of the delayed implantation. A combined an alysis of these experiments showed specific up-regulation of 27 genes both at the implantation site and during uterine activation, representing a broa d diversity of molecular functions. In contrast, the majority of genes that were decreased in the combined analysis were related to host immunity or t he immune response, suggesting the importance of these genes in regulating the uterine environment for the implanting blastocyst. Collectively, we ide ntified genes with recognized roles in implantation, genes with potential r oles in this process, and genes whose functions have yet to be defined in t his event. The identification of unique genetic markers for the onset of im plantation signifies that genome-wide analysis coupled with functional assa ys is a promising approach to resolve the molecular pathways required for s uccessful implantation.