Effect of EGF-like peptides on the metabolism of <em>in vitro</em> matured oocytes and their associated cumulus cells — ASN Events

Effect of EGF-like peptides on the metabolism of in vitro matured oocytes and their associated cumulus cells (#142)

Dulama Richani 1 , Melanie L Sutton-McDowall 1 , Laura A Frank 1 , Jeremy G Thompson 1 , Robert B Gilchrist 1
  1. Robinson Institute, School of Paediatrics and Reproductive Health, Faculty of Health Sciences, University of Adelaide, Adelaide, SA, Australia

Oocyte in vitro maturation (IVM) is an ART that involves the maturation of cumulus cell-enclosed oocytes (COCs) that are then capable of fertilization, implantation, and fetal development. We have recently shown that the EGF-like peptide signalling cascade, essential to oocyte maturation and ovulation in vivo, is perturbed in mouse COCs undergoing IVM when matured with the common additives follicle stimulating hormone (FSH) and/or epidermal growth factor (EGF), and that supplementation of IVM with EGF-like peptides amphiregulin or epiregulin improves oocyte developmental competence. Here we aimed to determine whether EGF-like peptides alter COC metabolism, resulting in increased oocyte developmental competence. Immature 129/Sv mouse COCs underwent IVM in the presence of FSH, EGF, amphiregulin, epiregulin, betacellulin, or no treatment (control). Epiregulin supplementation significantly increased intra-oocyte FAD++ compared to control and significantly increased the REDOX ratio compared to FSH and control (p<0.05). Amphiregulin and epiregulin significantly (p<0.05) 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. COC glucose consumption and lactate production were significantly lower in the control group (p<0.001), however, there were no differences between COCs treated 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 β-O-linked glycosylation of proteins, compared to control or FSH (p<0.05), suggesting greater stimulation of HBP activity. In conclusion, findings from this study suggest that (i) EGF-like peptides, particularly epiregulin, induce more oocyte mitochondrial activity than EGF or FSH, possibly yielding more ATP production and (ii) EGF-like peptides and EGF induce greater activity of the HBP, enabling more hyaluronic acid synthesis and protein β-O-linked glycosylation, an important post-translational modification of proteins that regulates their activity.