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Oocyte 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 signaling is perturbed in mouse COCs undergoing IVM when matured with follicle-stimulating hormone (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 intraoocyte flavin adenine dinucleotide (FAD) and REDOX (reduction and oxidation) ratio compared to FSH and control. Amphiregulin and epiregulin significantly increased the …