Hum. Reprod. Advance Access originally published online on June 21, 2006
Human Reproduction 2006 21(10):2495-2513; doi:10.1093/humrep/del195
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Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes
1 Department of Anatomy 2 Department of Pathology 3 MRC Rosalind Franklin Centre for Genomics Research (RFCGR), Cambridge, UK 4 Present address: The Scottish Centre for Genomic Technology and Informatics, College of Medicine, The University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK
5 To whom correspondence should be addressed at: Department of Anatomy, Downing Street, Cambridge CB2 3DY, UK. E-mail: mhj21{at}cam.ac.uk
BACKGROUND: The molecular basis of changes underlying the altered sensitivity of the uterine luminal epithelium (LE) to the embryo over the peri-implantation period is not fully understood. METHODS: Microarray analysis was performed on purified LE isolated from the pseudo-pregnant mouse uterus at 12-h intervals from pre-receptivity through the implantation window to refractoriness. The aim was to identify genes whose expression changes in the LE during this period. RESULTS: A total of 447 transcripts were identified whose abundance changed more than 2-fold in the LE but which did not change in the underlying stroma (S) and glands. Six major patterns of changing expression were noted. Of the 447 genes, 140 were expressed in LE at least 15-fold higher than in S and glandular epithelium (GE) (101 of these more than 20-fold). Detailed spatiotemporal expression profiles were derived for several genes previously implicated in implantation (including Edg7, Ptgs1, Pla2g4a and Alox15). CONCLUSIONS: Functional changes in LE receptivity are characterized by changing constellations of gene expression. Pre-receptivity has a different molecular footprint to refractoriness. Because we have used the pseudo-pregnant mouse model, these changes are driven solely by endocrine signals rather than events downstream of embryo attachment. Some of these genes have been described in previous microarray studies on endometrium, but for the majority, this is the first time they have been implicated in implantation. The 140 genes enriched in the LE greatly expand the list of epithelial markers and provide many novel candidates for further studies to identify genes playing important roles in receptivity and embryo attachment.
Key words: embryo receptivity/implantation window/mice/microarray/uterine luminal epithelium
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