Submitted on November 13, 2008
Revised on February 2, 2009
Accepted on March 2, 2009
Role for cumulus cell produced EGF-like ligands during primate oocyte maturation in vitro
Jenna K Nyholt de Prada1, Young S Lee2, Keith E Latham2, Charles L Chaffin3, and Catherine A VandeVoort4*
1 UC Davis
2 Temple University School of Medicine
3 University of Maryland School of Medicine
4 University of California, Davis
* To whom correspondence should be addressed. E-mail: cavandevoort{at}ucdavis.edu.
The developmental competence of in vitro matured (IVM) rhesus macaque cumulus oocyte complexes (COCs) is deficient when compared to in vivo matured 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 yielded a lower percentage of embryos that developed to the blastocyst stage compared to 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 (AREG), epiregulin (EREG) and betacellulin (BTC) 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 media without prior knowledge of pathway activity.
