Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility

Abstract

Successful embryo implantation depends on the quality of the embryo, as well as on the receptivity of the endometrium. The aim of this study was to investigate the endometrial gene expression profile in women with unexplained infertility in comparison with fertile controls at the time of embryo implantation in order to find potential predictive markers of uterine receptivity and to identify the molecular mechanisms of infertility. High-density oligonucleotide gene arrays, comprising 44 000 gene targets, were used to define the endometrial gene expression profile in infertile (n 1⁄4 4) and fertile (n 1⁄4 5) women during the mid-secretory phase (day LH þ7). Microarray results were validated using real-time PCR. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal com- ponent analysis showed a clear distinction in endometrial gene expression between infertile and fertile women. In total we identified 145 sig- nificantly (.3-fold change) up-regulated and 115 down-regulated genes in infertile women versus controls. Via Database for Annotation, Visualization and Integrated Discovery functional analysis we detected a substantial number of dysregulated genes in the endometria of infertile women, involved in cellular localization (21.1%) and transport (18.8%) and transporter activity (13.1%) and with major localization in extra- cellular regions (19.2%). Ingenuity Pathways Analysis of the gene list showed dysregulation of gene pathways involved in leukocyte extravasation signalling, lipid metabolism and detoxification in the endometria of infertile women. In conclusion, endometrial gene expression in women with unexplained infertility at the time of embryo implantation is markedly different from that in fertile women. These results provide new infor- mation on genes and pathways that may have functional significance as regards to endometrial receptivity and subsequent embryo implantation.