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Hum. Reprod. Advance Access published online on May 28, 2009
Human Reproduction, doi:10.1093/humrep/dep191
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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

Oct-4 regulates the expression of Stella and Foxj2 at the Nanog locus: implications for the developmental competence of mouse oocytes

Maurizio Zuccotti1,7, Valeria Merico2, Lucia Sacchi3, Michele Bellone2, Thore C. Brink4, Mario Stefanelli3, Carlo Alberto Redi5, Riccardo Bellazzi3, James Adjaye4 and Silvia Garagna2,6,7

1 Sezione di Istologia ed Embriologia, Dipartimento di Medicina Sperimentale, Universita' degli Studi di Parma, Via Volturno 39, 43100 Parma, Italy 2 Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia Animale, Universita' degli Studi di Pavia, Pavia, Italy 3 Dipartimento di Informatica e Sistemistica, Universita' degli Studi di Pavia, Pavia, Italy 4 Molecular Embryology and Aging Group, Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, Germany 5 Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy 6 Centro di Ricerca Interdipartimentale di Ingegneria Tissutale and Centro di Eccellenza in Biologia Applicata, Universita' degli Studi di Pavia, Pavia, Italy

7 Correspondence address. E-mail: maurizio.zuccotti{at}unipr.it (M.Z.); silvia.garagna{at}unipv.it (S.G.)

BACKGROUND: Our knowledge of what determines the mammalian oocyte developmental competence is meagre. By comparing the transcriptional profiles of developmentally competent surrounded nucleolus (SN) and incompetent not surrounded nucleolus (NSN) mouse MII oocytes, we recently demonstrated that Oct-4 and Stella are key factors in the establishment of the oocytes' developmental competence.

METHODS: Using RT–PCR, microarray and immunocytochemistry assays, we analysed expression of genes and proteins in oocytes isolated throughout folliculogenesis and classified based on their SN- or NSN-type of chromatin organization.

RESULTS: We show that: (1) Oct-4 and Stella are expressed concurrently at the beginning of oocytes' growth and only in SN oocytes; (2) Germ Cell Nuclear Factor is a putative regulator of Oct-4 expression in MII oocytes; (3) the function of Oct-4 is directed at the Nanog locus, regulating the expression of Stella and Foxj2.

CONCLUSIONS: (1) A number of factors that act upstream and downstream of Oct-4 emerge as candidate players in the acquisition of the oocyte's developmental competence; (2) we define molecular markers that identify a specific group of ovarian oocytes (SN) that have a potential to acquire developmental competence; (3) the presence of SN and NSN oocytes in human ovaries extends the interest of these results to the field of human reproduction.

Key words: Oct-4/Nanog locus/oocyte/developmental competence/mouse

Submitted on December 24, 2008; resubmitted on April 27, 2009; accepted on April 30, 2009.


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