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牛卵丘-卵母细胞复合物体外成熟过程中的能量代谢紊乱会干扰囊胚的质量和代谢。

Energy metabolism disorders during in vitro maturation of bovine cumulus-oocyte complexes interfere with blastocyst quality and metabolism.

机构信息

Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637, Poznan, Poland.

Laboratory of Bioinformatics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704, Poznan, Poland.

出版信息

Dev Biol. 2024 May;509:51-58. doi: 10.1016/j.ydbio.2024.02.004. Epub 2024 Feb 10.

Abstract

Glucose and fatty acids (FA) metabolism disturbances during oocyte in vitro maturation (IVM) affect their metabolism and surrounding cumulus cells, but only inhibition of glucose metabolism decreases embryo culture efficiency. Therefore, the present experiment aimed to reveal if glucose or FA metabolism inhibition leads to the disruption of embryo developmental potential, and to characterize the metabolic landscape of embryos reaching the blastocyst stage. Inhibitors of glucose (IO + DHEA) or FA (ETOMOXIR) metabolism were applied during IVM, and the control group was matured under standard conditions. Blastocysts obtained from experimental and control groups were analyzed with regard to lipidome and metabolome (mass spectrometry), transcriptome (RNA-Seq) and fluorescence lipid droplets staining (BODIPY). We showed that inhibition of glucose and fatty acid metabolism leads to cellular stress response compromising the quality of preimplantation embryos. The inhibition of energy metabolism affects membrane fluidity as well as downregulates fatty acids biosynthesis and gene expression of trophectoderm cell line markers. Therefore, we conclude that oocyte maturation environment exerts a substantial effect on preimplantation development programming at cellular and molecular levels.

摘要

在卵母细胞体外成熟(IVM)过程中,葡萄糖和脂肪酸(FA)代谢紊乱会影响卵母细胞及其周围的卵丘细胞的代谢,但只有葡萄糖代谢的抑制才会降低胚胎培养效率。因此,本实验旨在揭示葡萄糖或 FA 代谢抑制是否会导致胚胎发育潜能的破坏,并描述达到囊胚阶段的胚胎的代谢特征。在 IVM 期间,应用葡萄糖(IO+DHEA)或 FA(ETOMOXIR)代谢抑制剂,对照组在标准条件下成熟。对实验组和对照组获得的囊胚进行脂质组学和代谢组学(质谱分析)、转录组学(RNA-Seq)和荧光脂滴染色(BODIPY)分析。我们发现,葡萄糖和脂肪酸代谢的抑制会导致细胞应激反应,从而降低胚胎的质量。能量代谢的抑制会影响膜的流动性,并下调脂肪酸生物合成以及滋养外胚层细胞系标记物的基因表达。因此,我们得出结论,卵母细胞成熟环境对细胞和分子水平的胚胎着床前发育编程有重要影响。

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