Role for cumulus cell-produced EGF-like ligands during primate oocyte maturation in vitro.
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.
Nyholt de Prada
Jenna K
JK
University of California, Davis, CA 95616, USA. cavandevoort@ucdavis.edu.
Lee
Young S
YS
Latham
Keith E
KE
Chaffin
Charles L
CL
VandeVoort
Catherine A
CA
D066258:Amphiregulin; D000818:Animals; D066259:Betacellulin; D054885:Cumulus Cells / Q000187:drug effects / Q000502:physiology*; D066255:EGF Family of Proteins; D047108:Embryonic Development / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D066260:Epiregulin; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro / Q000662:veterinary; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry / Q000662:veterinary; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D008253:Macaca mulatta / Q000502:physiology*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011247:Pregnancy; D011799:Quinazolines; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D015398:Signal Transduction; D020032:Tyrphostins / Q000494:pharmacology
C587848:AREG protein, human; D066258:Amphiregulin; C587851:BTC protein, human; D066259:Betacellulin; D066255:EGF Family of Proteins; C587880:EREG protein, human; D004791:Enzyme Inhibitors; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011799:Quinazolines; D012333:RNA, Messenger; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D066246:ErbB Receptors