The Robinson Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
Biol Reprod. 2010 Dec;83(6):909-18. doi: 10.1095/biolreprod.110.084145. Epub 2010 Aug 4.
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.
卵母细胞和胚胎的代谢与其随后的发育能力密切相关。脂质是细胞能量的有效来源，但人们对卵母细胞成熟和早期胚胎发育过程中的脂质代谢知之甚少。脂肪酸在线粒体中通过β-氧化产生 ATP，限速步骤由肉碱棕榈酰转移酶 I（CPT1B）催化，该过程还需要肉碱。我们试图研究β-氧化在卵母细胞成熟和植入前发育过程中的调节和作用。通过实时 RT-PCR 在小鼠卵丘-卵母细胞复合物（COCs）中评估 Cpt1b mRNA 的表达，在体内用人绒毛膜促性腺激素（5 IU）诱导卵母细胞成熟和排卵以及达到囊胚阶段的胚胎中增加。β-氧化，通过从 [(3)H]棕榈酸产生 (3)H 2 O 来测量，在用表皮生长因子（3 ng/ml）和卵泡刺激素（50 mIU/ml）体外诱导成熟后，显著高于不成熟的 COCs。通过评估在抑制或上调β-氧化后胚胎发育的速度来证明脂质代谢对卵母细胞发育能力和早期胚胎发育的重要性分别用 etomoxir（CPT1B 抑制剂）或 L-肉碱。在卵母细胞成熟或合子分裂过程中抑制β-氧化会损害随后的囊胚发育。相比之下，在卵母细胞成熟期间补充 L-肉碱可显著增加β-氧化，提高发育能力，并且在没有碳水化合物能量供应的情况下，可显著增加 2 细胞分裂。因此，肉碱是发育中的卵母细胞的重要辅助因子，脂肪酸是卵母细胞和胚胎发育的重要能量来源。
