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Am J Physiol Endocrinol Metab 296: E1049-E1058, 2009. First published March 10, 2009; doi:10.1152/ajpendo.90930.2008
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Role for cumulus cell-produced EGF-like ligands during primate oocyte maturation in vitro

Jenna K. Nyholt de Prada,1 Young S. Lee,2 Keith E. Latham,2 Charles L. Chaffin,3 and Catherine A. VandeVoort1,4

1California National Primate Research Center and the Molecular, Cellular and Integrative Physiology Graduate Group, University of California, Davis, California; 2The Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania; 3Department Obstetrics and Gynecology and Reproductive Sciences, University of Maryland, Baltimore, Maryland; 4Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, California

Submitted 13 November 2008 ; accepted in final form 2 March 2009

The developmental competence of in vitro-matured (IVM) rhesus macaque cumulus oocyte complexes (COCs) is deficient compared with in vivo-matured (IVM) oocytes. To improve oocyte quality and subsequent embryo development following IVM, culture conditions must be optimized. A series of experiments was undertaken to determine the role of epidermal growth factor (EGF) during IVM of rhesus macaque COCs. The addition of Tyrphostin AG-1478 (a selective inhibitor of the EGF receptor EGFR) to the IVM medium yielded fewer oocytes maturing to metaphase II of meiosis II (MII), decreased cumulus expansion, and a lower percentage of embryos that developed to the blastocyst stage compared with untreated IVM controls, indicating that EGFR activation is important for IVM maturation in the rhesus macaque. However, the addition of recombinant human EGF (r-hEGF) to the IVM medium did not enhance outcome. The expression of mRNAs encoding the EGF-like factors amphiregulin, epiregulin, and betacellulin in cumulus cells indicates that these factors produced by cumulus cells may be responsible for maximal EGFR activation during oocyte maturation, precluding any further effect of exogenous r-hEGF. Additionally, these results illustrate the potential futility of exogenous supplementation of IVM medium without prior knowledge of pathway activity.

rhesus monkey; follicle; ovary; gene expression; epidermal growth factor



Address for reprint requests and other correspondence: C. A. VandeVoort, California National Primate Research Center, Univ. of California, Davis, CA 95616 (E-mail: cavandevoort{at}ucdavis.edu)







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