In search of candidate genes critically expressed in the human endometrium during the window of implantation.
BACKGROUND
In this prospective randomized blinded clinical trial, we examined gene expression profiles of the human endometrium during the early and mid-luteal phases of the natural cycle.


METHODS
An endometrial biopsy was performed on day 16 (LH +3) or on day 21 (LH +8), followed by RNA extraction and microarray analysis using an Affymetrix HG-U95A microchip. Data analysis was carried out using pairwise multiple group comparison with the significance analysis of microarrays (SAM) software.


RESULTS
With a false discovery rate of 0, the analysis revealed that 107 genes were significantly and differently expressed (> or =2-fold) during the early versus the mid-luteal phase of the cycle. Forty-five of these genes have not been previously linked to endometrial receptivity. Validation of the microarray data was accomplished using semiquantitative RT-PCR. We demonstrated the presence of estrogen and progesterone response elements (ERE and PRE) by analysis of the 5'-flanking regions of a subset of differentially regulated genes.


CONCLUSIONS
Using a strict bioinformatics approach of microarray data, we demonstrated significant changes in candidate genes during the transition of the early to the mid-luteal phase of the human endometrium that may have functional significance for the opening and maintenance of the window of implantation.
Mirkin
S
S
The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Virginia 23507, USA.
Arslan
M
M
Churikov
D
D
Corica
A
A
Diaz
J I
JI
Williams
S
S
Bocca
S
S
Oehninger
S
S
D000328:Adult; D019295:Computational Biology; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone