Beta-Oxidation Is Essential for Mouse Oocyte Developmental Competence and Early Embryo Development1

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.

Does serum cause lipid-droplet accumulation in bovine embryos produced in vitro, during developmental days 1 to 4?

“…The lipid β-oxidation would be essential for embryonic development, as demonstrated by Dunning et al [19]. According to our observations, there is a negative association between the area covered by lipids and hooded mitochondria.…”

The impact of obesity on egg quality

“…The idea that embryos and oocytes have a "quiet" metabolism was proposed in 2002 [64] and the nutritional excess provided by a high-fat or nutrient-rich diet may alter the metabolism and development. While excess fat in diet may cause deleterious effects, there is evidence that normal betaoxidation of fatty acids occurs in oocytes and embryos and is necessary for development [65,66]. Oocytes do contain lipid droplets and their localization and expression of related genes changes during oocyte maturation in the mouse, suggesting a role for lipid droplets in normal development.…”

Developmental phases of individual mouse preimplantation embryos characterized by lipid signatures using desorption electrospray ionization mass spectrometry

“…The main FA breakdown pathway involves beta-oxidation in which FAs are degraded to acetyl-CoA fragments, which in their turn can be used as substrates for the mitochondrial Krebs cycle [12]. Inhibition of the beta-oxidation pathway by impairing the entry of activated FA into the mitochondria using the drug etomoxir (an inhibitor of carnitine palmitoyl tranferase I) decreases mouse oocyte maturation, zygote cleavage, and blastocyst development, suggesting that FAs are an important energy source in murine oocyte maturation and preimplantation development [13].…”