Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development

Kylie R. Dunning, Kara Cashman, Darryl L. Russell, Jeremy G. Thompson, Robert J. Norman, Rebecca L. Robker

Research output: Contribution to journalArticle

213 Citations (Scopus)

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 3H2O from [3H]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 betaoxidation 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.

Original languageEnglish
Pages (from-to)909-918
Number of pages10
JournalBiology of Reproduction
Volume83
Issue number6
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

Keywords

  • Beta-oxidation
  • CPT1B
  • Embryo development
  • Fatty acid oxidation
  • Oocyte maturation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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