Effect of epidermal growth factor-like peptides on the metabolism of in vitro- matured mouse oocytes and cumulus cells.
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 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 1) EGF-like peptides, particularly epiregulin, induce more oocyte mitochondrial activity than EGF or FSH and 2) 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.
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, The Robinson Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Dulama
D
Richani
Melanie L
ML
Sutton-McDowall
Laura A
LA
Frank
Robert B
RB
Gilchrist
Jeremy G
JG
Thompson
D000818:Animals; D001562:Benzimidazoles; D002232:Carbocyanines; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005456:Fluorescent Dyes; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006595:Hexosamines / Q000378:metabolism; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009243:NAD / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010455:Peptides / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction
D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006595:Hexosamines; D010455:Peptides; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D019344:Lactic Acid; D004815:Epidermal Growth Factor; D012313:RNA; D005640:Follicle Stimulating Hormone; D005947:Glucose
EGF; FSH; IVM; amphiregulin; epiregulin; glucose; metabolism; mitochondria; oocyte; β-O-linked glycosylation