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Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in bovine

Abstract : Oocyte meiotic maturation requires energy from various substrates including glucose, amino acids and lipids. Mitochondrial fatty acid (FA) beta-oxidation (FAO) in the oocyte is required for meiotic maturation, which is accompanied by differential expression of numerous genes involved in FA metabolism in surrounding cumulus cells (CC) in vivo. The objective was to elucidate components involved in FA metabolism in CC during oocyte maturation. Twenty-seven genes related to lipogenesis, lipolysis, FA transport and FAO were chosen from comparative transcriptome analysis of bovine CC before and after maturation in vivo. Using real time PCR, 22 were significantly up-regulated at different times of in vitro maturation (IVM) in relation to oocyte meiosis progression from germinal vesicle (GV) breakdown to metaphase-II. Proteins FA synthase, acetyl-Co-A carboxylase, carnitine palmitoyltransferase CPT1, perilipin 2 and FA binding protein FABP3 were detected by western blot and immunolocalized to CC and oocyte cytoplasm, with FABP3 concentrated around oocyte chromatin. By mass spectrometry, CC lipid profiling was shown to be different before and after IVM. FAO inhibitors etomoxir and mildronate dose-dependently decreased oocyte maturation rate in vitro. In terms of viability, cumulus enclosed oocytes were more sensitive to etomoxir than denuded oocytes. In CC, etomoxir (150μ M) led to down-regulation of lipogenesis genes and up-regulated lipolysis and FAO genes. Moreover, the number of lipid droplets decreased whereas several lipid species were more abundant compared to non-treated CC after IVM. In conclusion, FA metabolism in CC is important to maintain metabolic homeostasis and may influence meiosis progression and survival of enclosed oocytes.
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Submitted on : Tuesday, March 10, 2015 - 8:43:34 PM
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Laura Sanchez-Lazo, Daphné Brisard, Sébastien Elis, Virginie Maillard, Rustem Uzbekov, et al.. Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in bovine. Molecular Endocrinology -Baltimore-, 2014, 28 (9), pp.1502-1521. ⟨10.1210/me.2014-1049⟩. ⟨hal-01129856⟩



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