Mol. Hum. Reprod. Advance Access published online on June 6, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan036
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Gene expression in cultured endometrium from women with different outcomes following IVF.
Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, and University of Berne, Switzerland.
Correspondence: Nick A. Bersinger, Ph.D., University of Berne, Murtenstrasse 35, Berne, CH-3010, Switzerland., FAX: [+41] 31 63 20953, E-Mail: nick.bersinger{at}dkf.unibe.ch
Estradiol and progesterone are crucial for the acquisition of receptivity and the change in transcriptional activity of target genes in the implantation window. The aim of this study was to differentiate the regulation of genes in the endometrium of patients with recurrent implantation failure (IF) versus those who became pregnant after IVF treatment. Moreover, the effect of embryo-derived factors on endometrial transcriptional activity was studied. Nine women with known IVF outcome (IF, M=Miscarriage, OP=ongoing pregnancy) and undergoing hysteroscopy with endometrial biopsy were enrolled. Biopsies were taken during the midluteal phase. After culture in presence of embryo-conditioned IVF media, total RNA was extracted and submitted to reverse transcription, target cDNA synthesis, biotin labelling, fragmentation, and hybridisation using the Affymetrix Human Genome U133A 2.0 Chip. Differential expression of selected genes was re-analysed by quantitative PCR, in which the results were calculated as threshold cycle differences between the groups and normalised to GAPDH and β-actin. Differences were seen for several genes from endometrial tissue between the IF and the pregnancy groups, and when comparing OP with M, 1875 up- and 1807 downregulated genes were returned. Real-time PCR analysis confirmed upregulation for somatostatin, PLAP-2, mucin 4, and CD163, and downregulation of glycodelin, IL-24, CD69, leukaemia inhibitory factor, and prolactin receptor between Op and M. When the different embryo conditioned media were compared, no significant differential regulation could be demonstrated. Although microarray profiling may currently not be sensitive enough for studying the effects of embryo-derived factors on the endometrium, the observed differences in gene expression between M and OP, suggest that it will become an interesting tool for the identification of fertility relevant markers produced by the endometrium.
Key Words: Endometrium/Gene profiling/IVF/Miscarriage/Implantation failure
Submitted on February 23, 2008; resubmitted on May 30, 2008; accepted on June 2, 2008.
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