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Mol. Hum. Reprod. Advance Access published online on January 18, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gam088
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© The Author 2008. 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

Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis

Aafke P. A. van Montfoort1,4, Joep P.M. Geraedts2, John C.M. Dumoulin1, Alphons P.M. Stassen3, Johannes L.H. Evers1 and Torik A.Y. Ayoubi3

1Department of Obstetrics & Gynaecology, Research Institute Growth & Development (GROW), Academic Hospital Maastricht, The Netherlands 2Department of Clinical Genetics, Research Institute Growth & Development (GROW), Academic Hospital Maastricht, The Netherlands 3Department of Population Genetics, Genomics and Bioinformatics, University Maastricht, The Netherlands

4 To whom correspondence should be addressed. E-mail: avmn{at}sgyn.azm.nl

Besides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of IVF and more particular of elective single embryo transfer (eSET). Genome-wide gene expression in cumulus cells was studied, since these cells surround the oocyte inside the follicle and therefore possibly reflect oocyte developmental potential. Early cleavage (EC) was chosen as a parameter for embryo viability. Gene expression in cumulus cells from eight oocytes resulting in an EC embryo (EC-CC; n=8) and from eight oocytes resulting in a non-EC (NEC) embryo (NEC-CC; n=8) was analysed using microarrays (n=16). A total of 611 genes were differentially expressed (P < 0.01), mainly involved in cell cycle, angiogenesis, apoptosis, epidermal growth factor, fibroblast growth factor and platelet-derived growth factor signalling, general vesicle transport and chemokine and cytokine signalling. Of the 25 selected differentially expressed genes analysed by quantitative real-time PCR (qRT-PCR) 15 (60%) genes could be validated in the original samples. Of these 8 (53%) could also be validated in 24 (12-EC-CC and 12 NEC-CC) extra independent samples. The most differentially expressed genes among these were CCND2, CXCR4 , GPX3 , CTNND1 DHCR7 , DVL3 , HSPB1 and TRIM28 , which probably point to hypoxic conditions or a delayed oocyte maturation in NEC-CC samples. This opens up perspectives for new molecular embryo or oocyte selection parameters which might also be useful in countries where the selection has to be made at the oocyte stage before fertilization instead of at the embryonic stage.

Key Words: assisted reproductive technology/early cleavage/gene expression/cumulus cells/microarray

Submitted on September 19, 2007; resubmitted on November 6, 2007; accepted on November 27, 2007.


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