Endometrial gene expression reveals compromised progesterone signaling in women refractory to embryo implantation

Abstract

Background: 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. Methods: Seventeen 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. Results: Transcriptome 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 A. Conclusions: We 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.

Background: 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. Methods: Seventeen 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. Results: Transcriptome 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 A. Conclusions: We 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.