Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia.
Development and Stem Cells Program, Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Genes (Basel). 2024 Mar 16;15(3):367. doi: 10.3390/genes15030367.
Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O) altered both aspects of mitochondrial function: the mtDNA copy number was upregulated in ICM, while MMP was diminished in TE. Embryos cultured in 20% O also exhibited delayed development kinetics, impaired implantation, and reduced mtDNA levels in E18 fetal liver. A model of oocyte mitochondrial stress using rotenone showed only a modest effect on on-time development and did not alter the mtDNA copy number in ICM; however, following embryo transfer, mtDNA was higher in the fetal heart. Lastly, endogenous mitochondrial dysfunction, induced by maternal age and obesity, altered the blastocyst mtDNA copy number, but not within the ICM. These results demonstrate that mitochondrial activity and mtDNA content exhibit cell-specific changes and are differentially responsive to diverse types of oxidative stress during pre-implantation embryogenesis.
线粒体在胚胎植入前发育过程中会发生多种变化，包括活性水平和线粒体 DNA（mtDNA）复制的转变。然而，这些不同方面的线粒体功能是如何联系的，以及它们对不同应激源的反应性还不是很清楚。在这里，我们表明，mtDNA 含量在 8 细胞胚胎和囊胚阶段之间增加，内细胞团（ICM）和滋养外胚层（TE）中的每个细胞的拷贝数相似。相比之下，TE 中的线粒体膜电位（MMP）高于 ICM。在常氧（20% O）中培养会改变线粒体功能的两个方面：ICM 中的 mtDNA 拷贝数上调，而 TE 中的 MMP 减少。在 20% O 中培养的胚胎也表现出发育动力学延迟、植入受损和 E18 胎肝中的 mtDNA 水平降低。使用鱼藤酮的卵母细胞线粒体应激模型仅对按时发育产生适度影响，并且不会改变 ICM 中的 mtDNA 拷贝数；然而，在胚胎移植后，胎儿心脏中的 mtDNA 更高。最后，母体年龄和肥胖引起的内源性线粒体功能障碍改变了囊胚 mtDNA 拷贝数，但 ICM 内没有改变。这些结果表明，线粒体活性和 mtDNA 含量表现出细胞特异性变化，并在胚胎植入前发育过程中对不同类型的氧化应激有不同的反应。
