title: Amphiregulin co-operates with bone morphogenetic protein 15 to increase bovine oocyte developmental competence: effects on gap junction-mediated metabolite supply.
abstract: This study assessed the participation of amphiregulin (AREG) and bone morphogenetic protein 15 (BMP15) during maturation of bovine cumulus-oocyte complexes (COCs) on cumulus cell function and their impact on subsequent embryo development. AREG treatment of COCs enhanced blastocyst formation and quality only when in the presence of BMP15. Expression of hyaluronan synthase 2 was enhanced by follicle-stimulating hormone (FSH) but not by AREG, which was reflected in the level of cumulus expansion. Although both FSH and AREG stimulated glycolysis, AREG-treated COCs had higher glucose consumption, lactate production and ratio of lactate production to glucose uptake. Autofluorescence levels in oocytes, indicative of NAD(P)H and FAD(++), were increased with combined AREG and BMP15 treatment of COCs. In contrast, these treatments did not alter autofluorescence levels when cumulus cells were removed from oocytes, even in the presence of other COCs, suggesting that oocyte-cumulus gap-junctional communication (GJC) is required. FSH contributed to maintaining GJC for an extended period of time. Remarkably, BMP15 was equally effective at maintaining GJC even in the presence of AREG. Hence, AREG stimulation of COC glycolysis and BMP15 preservation of GJC may facilitate efficient transfer of metabolites from cumulus cells to the oocyte thereby enhancing oocyte developmental competence. These results have implications for improving in vitro oocyte maturation systems.
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia Institute of Agriculture, Department of Biological Production, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugimura
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Ritter
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Sutton-McDowall
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Mottershead
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Thompson
authors.affiliation: Research Centre for Reproductive Health, The Robinson Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA 5005, Australia Discipline of Obstetrics and Gynaecology, School of Women's and Children's Health, Royal Hospital for Women, University of New South Wales, Kensington, NSW 2052, Australia r.gilchrist@unsw.edu.au.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gilchrist
mesh_terms: D066258:Amphiregulin / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D055430:Bone Morphogenetic Protein 15 / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D059471:In Vitro Oocyte Maturation Techniques; D019344:Lactic Acid / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D015398:Signal Transduction
chemical_list: D066258:Amphiregulin; D055430:Bone Morphogenetic Protein 15; D019344:Lactic Acid; D005640:Follicle Stimulating Hormone; D014453:Glucuronosyltransferase; D005947:Glucose
keywords: BMP15; amphiregulin; cumulus-oocyte complex; gap-junction; metabolism