Beta-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development

被引:342
作者
Dunning, Kylie R. [1 ]
Cashman, Kara [1 ]
Russell, Darryl L. [1 ]
Thompson, Jeremy G. [1 ]
Norman, Robert J. [1 ]
Robker, Rebecca L. [1 ]
机构
[1] Univ Adelaide, Robinson Inst, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia
基金
英国医学研究理事会;
关键词
beta-oxidation; CPT1B; embryo development; fatty acid oxidation; oocyte maturation; IN-VITRO MATURATION; FATTY-ACID OXIDATION; ENERGY-METABOLISM; GENE-EXPRESSION; MITOCHONDRIAL DISTRIBUTION; PREIMPLANTATION EMBRYOS; FOLLICULAR-FLUID; BOVINE OOCYTES; ATP CONTENT; CUMULUS;
D O I
10.1095/biolreprod.110.084145
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (H2O)-H-3 from [H-3]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 mlU/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.
引用
收藏
页码:909 / 918
页数:10
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