Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, 32-083 Kraków, Poland.
Int J Mol Sci. 2021 Mar 18;22(6):3099. doi: 10.3390/ijms22063099.
The effectiveness of somatic cell nuclear transfer (SCNT) in mammals seems to be still characterized by the disappointingly low rates of cloned embryos, fetuses, and progeny generated. These rates are measured in relation to the numbers of nuclear-transferred oocytes and can vary depending on the technique applied to the reconstruction of enucleated oocytes. The SCNT efficiency is also largely affected by the capability of donor nuclei to be epigenetically reprogrammed in a cytoplasm of reconstructed oocytes. The epigenetic reprogrammability of donor nuclei in SCNT-derived embryos appears to be biased, to a great extent, by the extranuclear (cytoplasmic) inheritance of mitochondrial DNA (mtDNA) fractions originating from donor cells. A high frequency of mtDNA heteroplasmy occurrence can lead to disturbances in the intergenomic crosstalk between mitochondrial and nuclear compartments during the early embryogenesis of SCNT-derived embryos. These disturbances can give rise to incorrect and incomplete epigenetic reprogramming of donor nuclei in mammalian cloned embryos. The dwindling reprogrammability of donor nuclei in the blastomeres of SCNT-derived embryos can also be impacted by impaired epigenetic rearrangements within terminal ends of donor cell-descended chromosomes (i.e., telomeres). Therefore, dysfunctions in epigenetic reprogramming of donor nuclei can contribute to the enhanced attrition of telomeres. This accelerates the processes of epigenomic aging and replicative senescence in the cells forming various tissues and organs of cloned fetuses and progeny. For all the above-mentioned reasons, the current paper aims to overview the state of the art in not only molecular mechanisms underlying intergenomic communication between nuclear and mtDNA molecules in cloned embryos but also intrinsic determinants affecting unfaithful epigenetic reprogrammability of telomeres. The latter is related to their abrasion within somatic cell-inherited chromosomes.
哺乳动物体细胞核移植 (SCNT) 的有效性似乎仍然受到克隆胚胎、胎儿和后代生成率低的困扰。这些比率是相对于核转移卵母细胞的数量来衡量的，并且可能因应用于去核卵母细胞重建的技术而有所不同。SCNT 效率也在很大程度上受到供体核在重建卵母细胞质中被表观遗传重新编程的能力的影响。供体核在 SCNT 衍生胚胎中的表观遗传可重编程性似乎在很大程度上受到源自供体细胞的线粒体 DNA (mtDNA) 分数的核外（细胞质）遗传的影响。mtDNA 异质性的高频发生可能导致 SCNT 衍生胚胎早期胚胎发生过程中线粒体和核区室之间的基因组间串扰发生紊乱。这些干扰可能导致哺乳动物克隆胚胎中供体核的不正确和不完全的表观遗传重编程。供体核在 SCNT 衍生胚胎的卵裂球中的重编程能力下降也可能受到供体细胞衍生染色体末端（即端粒）内表观遗传重排的损害的影响。因此，供体核的表观遗传重编程功能障碍可能导致端粒加速消耗。这加速了形成克隆胎儿和后代各种组织和器官的细胞中表观基因组衰老和复制性衰老的过程。基于所有上述原因，本文旨在概述不仅在核和 mtDNA 分子之间的基因组间通讯的分子机制方面，而且还在影响端粒的不忠实表观遗传可重编程性的内在决定因素方面的最新进展。后者与它们在体细胞继承染色体内的磨损有关。
