Bowles Emma J, Campbell Keith H S, St John Justin C
The Mitochondrial and Reproductive Genetics Group, The Division of Medical Sciences, The Medical School, The University of Birmingham, Birmingham B15 2TT, United Kingdom.
Curr Top Dev Biol. 2007;77:251-90. doi: 10.1016/S0070-2153(06)77010-7.
Nuclear transfer technology has uses across theoretical and applied applications, but advances are restricted by continued poor success rates and health problems associated with live offspring. Development of reconstructed embryos is dependent upon numerous interlinking factors relating both to the donor cell and the recipient oocyte. For example, abnormalities in gene expression following somatic cell nuclear transfer (SCNT) have been linked with an inability of the oocyte cytoplasm to sufficiently epigenetically reprogram the nucleus. Furthermore, influences on the propagation of mitochondria and mitochondrial DNA (mtDNA) could be of great importance in determining the early developmental potential of NT embryos and contributing to their genetic identity. mtDNA encodes some of the subunits of the electron transfer chain, responsible for cellular ATP production. The remaining subunits and those factors required for mtDNA replication, transcription and translation are encoded by the nucleus, necessitating precise intergenomic communication. Additionally, regulation of mtDNA copy number, via the processes of mtDNA transcription and replication, is essential for normal preimplantation embryo development and differentiation. Unimaternal transmission following natural fertilization usually results in the presence of a single identical population of mtDNA, homoplasmy. Heteroplasmy can result if mixed populations of mtDNA genomes co-exist. Many abnormalities observed in NT embryos, fetuses, and offspring may be caused by deficiencies in OXPHOS, perhaps resulting in part from heteroplasmic mtDNA populations. Additionally, incompatibilities between the somatic nucleus and the cytoplast may be exacerbated by increased genetic divergence between the two genomes. It is important to ensure that the nucleus is capable of sufficiently regulating mtDNA, requiring a level of compatibility between the two genomes, which may be a function of evolutionary distance. We suggest that abnormal expression of factors such as TFAM and POLG in NT embryos will prematurely drive mtDNA replication, hence impacting on early development.
核移植技术在理论和应用领域都有应用，但进展受到持续较低的成功率以及与活体后代相关的健康问题的限制。重构胚胎的发育取决于许多与供体细胞和受体卵母细胞相关的相互关联的因素。例如，体细胞核移植（SCNT）后基因表达异常与卵母细胞细胞质无法充分对细胞核进行表观遗传重编程有关。此外，线粒体和线粒体DNA（mtDNA）的传播影响对于确定核移植胚胎的早期发育潜力及其遗传特性可能非常重要。mtDNA编码电子传递链的一些亚基，负责细胞ATP的产生。其余亚基以及mtDNA复制、转录和翻译所需的那些因子由细胞核编码，这需要精确的基因组间通讯。此外，通过mtDNA转录和复制过程对mtDNA拷贝数的调节对于正常的植入前胚胎发育和分化至关重要。自然受精后的单亲遗传通常导致单一相同的mtDNA群体存在，即同质性。如果mtDNA基因组的混合群体共存，则可能导致异质性。在核移植胚胎、胎儿和后代中观察到的许多异常可能是由氧化磷酸化缺陷引起的，这可能部分是由异质性mtDNA群体导致的。此外，体细胞核与细胞质体之间的不相容性可能会因两个基因组之间遗传差异的增加而加剧。确保细胞核能够充分调节mtDNA很重要，这需要两个基因组之间具有一定程度的兼容性，这可能是进化距离的函数。我们认为，核移植胚胎中TFAM和POLG等因子的异常表达会过早驱动mtDNA复制，从而影响早期发育。
