Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure.
BACKGROUND
Repeated implantation failure (RIF) is a severe obstacle in human assisted reproduction treatment.


METHODS
Aiming to identify global gene profile in RIF patients, gene-array analyses were performed on endometrial samples collected on day 21 of the cycle from fertile women (n = 12) and from RIF patients (n = 20). Validation of cyclin E2, Slug, dickkopf homolog 1 (DKK1), lymphoid enhancer-binding factor 1 (LEF1) and secreted frizzled-related protein 1 (SFRP1) was carried out by real-time PCR.


RESULTS
Gene-array analysis revealed 313 genes exhibiting modified expression levels in RIF patients. Of these, 288 genes (92%) were down-regulated and only 25 genes (8%) were up-regulated. Classification of the down-regulated genes to biological pathways revealed cell cycle, Wnt signaling and cellular adhesion pathways. Real-time PCR validation of cyclin E2, SFRP1 and LEF1 showed significantly lower expression levels in RIF-IVF patients as compared with fertile women. In addition, two up-regulated genes, Slug and DKK1, were also validated. Interestingly, about 8% of the down-regulated genes were estrogen-dependent. Western blot of estrogen receptor alpha revealed low expression of this protein in the RIF group.


CONCLUSIONS
The evaluation of the endometrium of RIF patients by gene array analysis demonstrates that the expression of various genes is altered, including those belonging to the cell cycle, Wnt signaling and cellular adhesion pathways.
Koler
Moriah
M
Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem 91120, Israel.
Achache
Hanna
H
Tsafrir
Avi
A
Smith
Yoav
Y
Revel
Ariel
A
Reich
Reuven
R
D000328:Adult; D016000:Cluster Analysis; D010064:Embryo Implantation / Q000235:genetics; D004717:Endometrium / Q000378:metabolism; D004967:Estrogens / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction
D004967:Estrogens