Open Access Research article

Transcriptome based identification of mouse cumulus cell markers that predict the developmental competence of their enclosed antral oocytes

Giulia Vigone1, Valeria Merico1, Alessandro Prigione2, Francesca Mulas3, Lucia Sacchi4, Matteo Gabetta4, Riccardo Bellazzi34, Carlo Alberto Redi1, Giuliano Mazzini5, James Adjaye26*, Silvia Garagna137* and Maurizio Zuccotti8*

Author Affiliations

1 Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie ‘Lazzaro Spallanzani’, Universita’ degli Studi di Pavia, Pavia, Italy

2 Department of Vertebrate Genomics. Max-Planck Institute for Molecular Genetics, Molecular Embryology and Aging Group, Berlin, Germany

3 Centro di Ingegneria Tissutale, Universita’ degli Studi di Pavia, Pavia, Italy

4 Dipartimento di Ingegneria Industriale e dell’Informazione, Universita’ degli Studi di Pavia, Pavia, Italy

5 Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, Via Ferrata 9, Pavia, Italy

6 Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

7 Centro di Eccellenza in Biologia Applicata, Universita’ degli Studi di Pavia, Pavia, Italy

8 Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali (S.Bi.Bi.T.), Sezione di Anatomia, Istologia ed Embriologia, Universita’ degli Studi di Parma, Via Volturno, Parma, 39-43125, Italy

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BMC Genomics 2013, 14:380  doi:10.1186/1471-2164-14-380

Published: 7 June 2013

Abstract

Background

The cumulus cells (CCs) enveloping antral and ovulated oocytes have been regarded as putative source of non-invasive markers of the oocyte developmental competence. A number of studies have indeed observed a correlation between CCs gene expression, embryo quality, and final pregnancy outcome. Here, we isolated CCs from antral mouse oocytes of known developmental incompetence (NSN-CCs) or competence (SN-CCs) and compared their transcriptomes with the aim of identifying distinct marker transcripts.

Results

Global gene expression analysis highlighted that both types of CCs share similar transcriptomes, with the exception of 422 genes, 97.6% of which were down-regulated in NSN-CCs vs. SN-CCs. This transcriptional down-regulation in NSN-CCs was confirmed by qRT-PCR analysis of CC-related genes (Has2, Ptx3, Tnfaip6 and Ptgs2). Only ten of the 422 genes were up-regulated with Amh being the most up-regulated in NSN-CCs, with an average 4-fold higher expression when analysed by qRT-PCR.

Conclusions

The developmental incompetence (NSN) or competence (SN) of antral oocytes can be predicted using transcript markers expressed by their surrounding CCs (i.e., Has2, Ptx3, Tnfaip6, Ptgs2 and Amh). Overall, the regulated nature of the group of genes brought out by whole transcriptome analysis constitutes the molecular signature of CCs associated either with developmentally incompetent or competent oocytes and may represent a valuable resource for developing new molecular tools for the assessment of oocyte quality and to further investigate the complex bi-directional interaction occurring between CCs and oocyte.

Keywords:
Oocyte; Developmental competence; Cumulus cells; Transcriptome