Laboratory of Animal Genetics and Reproduction, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido, 060-8589, Japan.
Hokkaido Agricultural Research Center, NARO, Sapporo, Hokkaido, 062-8555, Japan.
Sci Rep. 2023 Dec 27;13(1):23058. doi: 10.1038/s41598-023-50444-2.
Heteroplasmic mammalian embryos between genetically distant species fail to develop to term, preventing transmission of xenomitochondrial DNA to progeny. However, there is no direct evidence indicating the mechanisms by which species specificity of the mitochondrial genome is ensured during mammalian development. Here, we have uncovered a two-step strategy underlying the prevention of xenomitochondrial DNA transmission in mouse embryos harboring bovine mitochondria (mtB-M embryos). First, mtB-M embryos showed metabolic disorder by transient increase of reactive oxygen species at the 4-cell stage, resulting in repressed development. Second, trophoblasts of mtB-M embryos led to implantation failure. Therefore, we tested cell aggregation with tetraploid embryos to compensate for the placentation of mtB-M embryos. The 14 mtB-M embryos harboring bovine mtDNAs developed to term at embryonic day 19.5. Taken together, our results show that contamination of bovine mtDNA is prohibited by embryonic lethality due to metabolic disruption and failure of placentation, suggesting these represent xenomitochondrial elimination mechanisms in mammalian embryos.
遗传上远缘的种间杂种哺乳动物胚胎不能发育至足月，阻止了异种线粒体 DNA 向后代的传递。然而，目前尚无直接证据表明在哺乳动物发育过程中，线粒体基因组的种属特异性是如何得到保证的。在这里，我们揭示了防止携带牛线粒体（mtB-M 胚胎）的小鼠胚胎中异种线粒体 DNA 传递的两步策略。首先，mtB-M 胚胎在 4 细胞阶段通过活性氧的短暂增加表现出代谢紊乱，导致发育受阻。其次，mtB-M 胚胎的滋养层导致着床失败。因此，我们用四倍体胚胎进行细胞聚集实验，以补偿 mtB-M 胚胎的胎盘形成。14 个携带牛 mtDNA 的 mtB-M 胚胎在胚胎第 19.5 天发育至足月。总之，我们的结果表明，由于代谢紊乱和胎盘形成失败导致胚胎致死性，牛 mtDNA 的污染受到了限制，这表明这些代表了哺乳动物胚胎中异种线粒体的消除机制。
