title: Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development.
abstract: Oocyte and embryo metabolism are closely linked with their subsequent developmental capacity. Lipids are a potent source of cellular energy, yet little is known about lipid metabolism during oocyte maturation and early embryo development. Generation of ATP from lipids occurs within mitochondria via beta-oxidation of fatty acids, with the rate-limiting step catalyzed by carnitine palmitoyl transferase I (CPT1B), a process also requiring carnitine. We sought to investigate the regulation and role of beta-oxidation during oocyte maturation and preimplantation development. Expression of Cpt1b mRNA, assessed by real-time RT-PCR in murine cumulus-oocyte complexes (COCs), increased following hormonal induction of oocyte maturation and ovulation in vivo with human chorionic gonadotropin (5 IU) and in embryos reaching the blastocyst stage. Beta-oxidation, measured by the production of (3)H(2)O from [(3)H]palmitic acid, was significantly increased over that in immature COCs following induction of maturation in vitro with epidermal growth factor (3 ng/ml) and follicle-stimulating hormone (50 mIU/ml). The importance of lipid metabolism for oocyte developmental competence and early embryo development was demonstrated by assessing the rate of embryo development following inhibition or upregulation of beta-oxidation with etomoxir (an inhibitor of CPT1B) or L-carnitine, respectively. Inhibition of beta-oxidation during oocyte maturation or zygote cleavage impaired subsequent blastocyst development. In contrast, L-carnitine supplementation during oocyte maturation significantly increased beta-oxidation, improved developmental competence, and in the absence of a carbohydrate energy supply, significantly increased 2-cell cleavage. Thus, carnitine is an important cofactor for developing oocytes, and fatty acids are an important energy source for oocyte and embryo development.
authors.affiliation: The Robinson Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia. kylie.dunning@adelaide.edu.au
authors.forename: Kylie R
authors.initials: KR
authors.lastname: Dunning
authors.forename: Kara
authors.initials: K
authors.lastname: Cashman
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Russell
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Thompson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D009866:Oogenesis / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015053:Zygote / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005227:Fatty Acids; D012333:RNA, Messenger; C558401:CPT1B protein, mouse; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine