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Hum. Reprod. Advance Access published online on June 19, 2009
Human Reproduction, doi:10.1093/humrep/dep193
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure

Moriah Koler1,{dagger}, Hanna Achache1,{dagger}, Avi Tsafrir2, Yoav Smith3, Ariel Revel2,4 and Reuven Reich1,{ddagger}

1 Department of Pharmacology, School of Pharmacy, Hebrew University, Jerusalem 91120, Israel 2 Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem 91120, Israel 3 Bioinformatics Units, Hebrew University, Jerusalem, Israel

4 Correspondence address. Tel: +972-6776424-2-972; Fax: +972-6433337-2-972; E-mail: arielrevel2{at}gmail.com

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.

Key words: gene-array/female infertility/implantation-array/implantation

{dagger} These two authors have equally contributed to this work.

{ddagger} R.R. is affiliated with the David R. Bloom Center for Pharmacy at the Hebrew University.

Submitted on October 9, 2008; resubmitted on April 23, 2009; accepted on May 1, 2009.


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