Effect of lipotoxicity on mitochondrial function and epigenetic programming during bovine in vitro embryo production.
Effect of lipotoxicity on mitochondrial function and epigenetic programming during bovine in vitro embryo production.
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DOI：
10.1038/s41598-023-49184-0
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发表时间：
2023-12-08
影响因子：
4.6
通讯作者：
Leroy, Jo L. M. R.
中科院分区：
文献类型：
--
作者：
Meulders, Ben;Marei, Waleed F. A.;Xhonneux, Inne;Bols, Peter E. J.;Leroy, Jo L. M. R.
母体代谢紊乱可能会对发育中的卵母细胞造成脂毒性作用。了解这可能扰乱胚胎表观遗传编程的时间以及这与线粒体功能障碍的关系对于改进辅助生殖治疗至关重要，但以前还没有进行过研究。因此，我们使用牛的体外模型来研究在体外卵母细胞成熟和体外胚胎培养过程中，与对照(CONT)和溶剂对照(SCONT)相比，体外卵母细胞成熟和体外胚胎培养过程中的病理生理棕榈酸(PA)浓度是否改变了胚胎的表观遗传模式(DNA甲基化(5mC)和组蛋白乙酰化/甲基化(H3K9ac/H3K9me2))。其次，我们调查了这些表观遗传改变是否与线粒体功能障碍和ATP生成率的变化有关，或者是否与表观遗传调控基因的表达改变有关。与SCONT相比，PA来源的受精卵中H3K9ac和H3K9me2的水平升高。此外，与SCONT相比，暴露于PA的桑椹胚中5mC和H3K9me2的水平也升高。这与PA对卵母细胞糖酵解ATP生成的完全抑制、4-细胞胚胎线粒体膜电位的增加和糖酵解ATP生成的完全抑制以及受精卵和桑椹胚中SOD2表达的减少有关。在同一项研究中，首次观察到代谢受损的受精卵和桑椹胚的表观遗传学变化与线粒体功能障碍并行。
Maternal metabolic disorders may cause lipotoxic effects on the developing oocyte. Understanding the timing at which this might disrupt embryo epigenetic programming and how this is linked with mitochondrial dysfunction is crucial for improving assisted reproductive treatments, but has not been investigated before. Therefore, we used a bovine in vitro model to investigate if pathophysiological palmitic acid (PA) concentrations during in vitro oocyte maturation and in vitro embryo culture alter embryo epigenetic patterns (DNA methylation (5mC) and histone acetylation/methylation (H3K9ac/H3K9me2)) compared to control (CONT) and solvent control (SCONT), at the zygote and morula stage. Secondly, we investigated if these epigenetic alterations are associated with mitochondrial dysfunction and changes in ATP production rate, or altered expression of epigenetic regulatory genes. Compared to SCONT, H3K9ac and H3K9me2 levels were increased in PA-derived zygotes. Also, 5mC and H3K9me2 levels were increased in PA-exposed morulae compared to SCONT. This was associated with complete inhibition of glycolytic ATP production in oocytes, increased mitochondrial membrane potential and complete inhibition of glycolytic ATP production in 4-cell embryos and reduced SOD2 expression in PA-exposed zygotes and morulae. For the first time, epigenetic alterations in metabolically compromised zygotes and morulae have been observed in parallel with mitochondrial dysfunction in the same study.
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影响因子：
2.1
作者：
Jordaens, Lies;Van Hoeck, Veerle;Leroy, Jo L. M. R.
通讯作者：
Leroy, Jo L. M. R.
影响因子：
3.8
作者：
Komatsu, Kouji;Iwase, Akira;Kikkawa, Fumitaka
通讯作者：
Kikkawa, Fumitaka
影响因子：
6.1
作者：
Bermejo-Alvarez, Pablo;Rosenfeld, Cheryl S.;Roberts, R. Michael
通讯作者：
Roberts, R. Michael
DOI：
10.1073/pnas.1321569111
发表时间：
2014-03-18
影响因子：
11.1
作者：
Graf, Alexander;Krebs, Stefan;Wolf, Eckhard
通讯作者：
Wolf, Eckhard
影响因子：
4
作者：
Fan, Jing;Krautkramer, Kimberly A.;Feldman, Jessica L.;Denu, John M.
通讯作者：
Denu, John M.