Abstract
BackgroundEndometrial function is essential for embryo implantation. The aim of this study was to analyze gene expression profiles from individual endometrial samples obtained from women with repeated implantation failure after IVF in oocyte donation programs.MethodsSeventeen volunteers were recruited: women who had previously participated as recipients in oocyte donation cycles and repeatedly exhibited implantation failure (Group A, study group, n = 5) or had at least one successful cycle (Group B, control group, n = 6) and spontaneously fertile women (Group C, normal fertility group, n = 6). An endometrial cycle was induced with exogenous estradiol (E2) and progesterone (P) and an endometrial sample was collected on the seventh day of P treatment.ResultsTranscriptome analysis showed 82 genes with consistent differential gene expression when comparing A vs. B and A vs. C. One hundred transcripts differentially expressed in group A vs. B have been shown to be regulated by P, suggesting compromised P signaling in the endometrium. The P receptor (PR) mutation PROGINS was not detected in women from group A. Semi-quantitation of immunoreactive PRA/B, PRB and Sp1 (a transcription factor related to P signaling) in paraffin-embedded endometrial sections, did not show statistically significant differences amongst groups. However immunostaining glycodelin was significantly decreased in endometrial samples from group AConclusionsWe conclude that some cases of repeated implantation failure could be associated with an aberrant gene expression profile. Compromised P signaling might be the underlying mechanism for such endometrial gene expression deregulation in women with repeated implantation failure.
Highlights
Endometrial function is essential for embryo implantation
Each point in a Principal component analysis (PCA) graph represents the gene expression profile of an endometrial sample and the distance between two plotted points is proportional to the degree of similarity between the gene expression profiles
Gene expression profiles from endometrial samples obtained from microarray analysis were subjected to unsupervised hierarchical clustering analysis in order to generate a dendogram, which is a tree-structured graph that illustrates the similarities in gene expression profiles between endometrial samples from all groups
Summary
Endometrial function is essential for embryo implantation. The aim of this study was to analyze gene expression profiles from individual endometrial samples obtained from women with repeated implantation failure after IVF in oocyte donation programs. The endometrial samples are collected during the time interval corresponding to the window of implantation [13] comparing gene expression profiles from women who were refractory to implantation and those who achieved pregnancy in previous oocyte donation cycles [12]. This previous study provided interesting insights to endometrial gene expression associated with implantation failure, the microarrays analysis was performed with only 3(from a total of 5) samples from women with repeated embryo implantation failure that were pooled and using a microarrays platform that examined only one-third of the human genome; providing only a partial view of the whole picture
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