Comparative Importance of Fatty Acid Beta-Oxidation to Nuclear Maturation, Gene Expression, and Glucose Metabolism in Mouse, Bovine, and Porcine Cumulus Oocyte Complexes

Comparative Importance of Fatty Acid Beta-Oxidation to Nuclear Maturation, Gene Expression, and Glucose Metabolism in Mouse, Bovine, and Porcine Cumulus Oocyte Complexes
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DOI:
10.1095/biolreprod.113.108548
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发表时间:
2013-05-01
影响因子:
3.6
通讯作者:
Krisher, Rebecca L.
Krisher, Rebecca L.
中科院分区:
生物学2区
文献类型:
--
作者:
Paczkowski, Melissa;Silva, Elena;Krisher, Rebecca L.

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本实验的目的是评估卵丘卵母细胞复合体(COC)体外成熟(IVM)过程中的脂肪酸β-氧化(FAO)对卵母细胞和卵丘细胞的核成熟和基因表达的重要性。在小鼠卵母细胞、牛卵母细胞和猪卵母细胞分别暴露于250 mU、100 mU和10 mU的依托莫西后,卵母细胞的核成熟均受到抑制(P<0.05)。当FAO在小鼠和猪的COCs中被抑制,导致减数分裂被抑制时,FAO、糖酵解和氧化应激基因在卵母细胞和卵丘细胞中的丰度降低(P<0.05),尽管在猪中的程度要大得多。在牛卵母细胞和卵丘细胞中,在依托莫西抑制减数分裂后,FAO基因转录增加,糖酵解基因表达发生改变。在不抑制牛和小鼠COCs核成熟的剂量下,etomoxir增加了葡萄糖消耗(P<0.05),这表明当脂肪酸代谢受损时,葡萄糖代谢会增加,以满足COCs的代谢需求。我们的数据表明,粮农组织对这三个物种的卵母细胞核成熟都是必不可少的。核成熟对粮农组织抑制的敏感性反映了卵质中存在的脂类的数量,并可能表明对这一代谢途径的相对依赖。
The objective of these experiments was to evaluate the importance of fatty acid beta-oxidation (FAO) in the cumulus oocyte complex (COC) during in vitro maturation (IVM) to oocyte nuclear maturation and gene expression in both the oocyte and cumulus cells in three species with differing amounts of oocyte intracellular lipids (mouse, low; bovine, moderate; porcine, high). We inhibited FAO using etomoxir at 0, 10, 25, 100, or 250 mu M. Completion of oocyte nuclear maturation was inhibited after COC exposure to 250 mu M etomoxir in mouse oocytes, 100 mu M etomoxir in bovine oocytes, and as little as 10 mu M etomoxir in porcine oocytes (P < 0.05). When FAO was inhibited in mouse and porcine COCs resulting in inhibition of meiosis, the abundance of FAO, glycolytic, and oxidative stress gene transcripts were decreased in oocytes and cumulus cells (P < 0.05), although to a much greater extent in the pig. In bovine oocytes and cumulus cells, FAO gene transcripts were increased and glycolytic gene expression altered following meiotic inhibition due to etomoxir. Etomoxir, at doses that did not inhibit nuclear maturation in bovine and murine COCs, increased glucose consumption (P < 0.05), suggesting glucose metabolism is increased to meet the metabolic demands of the COCs when fatty acid metabolism is compromised. Our data demonstrates that FAO is essential to oocyte nuclear maturation in all three species. Sensitivity of nuclear maturation to FAO inhibition reflects the amount of lipid present in the ooplasm and may suggest a relative reliance on this metabolic pathway.