Richani, D.Sutton-McDowall, M.Frank, L.Gilchrist, R.Thompson, J.2014-02-062014-02-062014Biology of Reproduction, 2014; 90(3):49-490006-33631529-7268http://hdl.handle.net/2440/81927Oocyte in vitro maturation (IVM) is an assisted reproductive technology that involves the maturation of cumulus-oocyte-complexes (COCs) that are then capable of normal development. We have shown that epidermal growth factor (EGF)-like peptide signalling is perturbed in mouse COCs undergoing IVM when matured with FSH and/or EGF, but supplementation of IVM with EGF-like peptides amphiregulin or epiregulin improves oocyte developmental competence. Here we aimed to determine whether EGF-like peptides regulate COC metabolism. Immature 129/Sv mouse COCs underwent IVM with FSH, EGF, amphiregulin, epiregulin, betacellulin, or no treatment (control). Epiregulin significantly increased intra-oocyte FAD++ and REDOX ratio compared to FSH and control. Amphiregulin and epiregulin significantly increased the proportion of J-aggregates (from JC-1) in oocyte mitochondria compared to control, FSH or EGF, and this coupled with FAD++ and REDOX measures indicates greater mitochondrial activity. There were no differences in glucose consumption, lactate production, or glycolysis between COCs matured with FSH, EGF and EGF-like peptides. COCs matured with EGF or EGF-like peptides exhibited significantly higher mRNA expression of the hexosamine biosynthesis pathway (HBP) rate-limiting enzyme gene Gfpt2, Has2 expression, and global beta-O-linked glycosylation of proteins, compared to control or FSH, suggesting greater HBP activity. Our findings suggest that; (i) EGF-like peptides, particularly epiregulin, induce more oocyte mitochondrial activity than EGF or FSH, and (ii) EGF-like peptides and EGF induce greater HBP activity, enabling more hyaluronic acid synthesis and protein beta-O-linked glycosylation. These metabolic alterations may be a mechanism by which EGF-like peptides increase oocyte developmental competence.enCopyright 2014 by The Society for the Study of Reproduction.Cumulus cellsGrowth factorsIn vitro maturation (IVM)MetabolismOocyte maturationJournal article00300001872014020610471310.1095/biolreprod.113.11531111 Medical and Health Sciences1114 Paediatrics and Reproductive Medicine111404 Reproduction0003326227000032-s2.0-8489994391164193Sutton-McDowall, M. [0000-0002-4121-0202]Gilchrist, R. [0000-0003-1611-7142]Thompson, J. [0000-0003-4941-7731]