Different fates of donor mitochondrial DNA in bovine-rabbit and cloned bovine-rabbit reconstructed embryos during preimplantation development
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China. Frontiers in Bioscience
(Impact Factor: 3.52).
02/2006; 11(1):1425-32. DOI: 10.2741/1893
The functions of mitochondria depend on precise interaction between nuclear and cytoplasmic genomes. Non-balance of mtDNA has been reported in most nuclear transfer embryos and offspring. The reason of the degradation of donor mtDNA is still not clear. To further investigate the mechanism, in this study, we designed an experiment as follows. Two fibroblast cell lines sharing same nuclear genome but different mitochondria genome backgrounds, namely cells from ear tissues of cloned bovine and its donor, were choose as donor cells and introduced into enucleated rabbit oocytes. Similar developmental potential was observed in cloned bovine-rabbit (clone group) and bovine-rabbit (non-clone group) embryos. Real-time PCR assay showed that, in non-clone group, bovine mtDNA decreased during the development of reconstructed embryo, and that a sharp decrease was detected at the blastocyst stage. In clone group, bovine mtDNA decreased slightly, and the abrupt reduction of donor mtDNA did not occur during preimplantation development. In addition, an obvious increase in rabbit mtDNA was observed in both groups at the blastocyst stage. Our results demonstrate that: 1) the fates of donor mtDNAs in bovine-rabbit and cloned bovine-rabbit reconstructed embryos were different; and 2) recipient mtDNAs replicate at blastocyst regardless of the difference of donor cells.
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- "However, development of canine–pig iSCNT blastocysts was reported in 2009 (Sugimura et al., 2009).Rabbit oocytes. Rabbit oocytes were found to be good recipients when shown to support preimplantation development of embryos derived from nuclei of several species, including bovine (Jiang et al., 2006), Capra ibex (Jiang et al., 2005), chicken (Liu et al., 2004), camel and Tibetan antelope (Zhao et al., 2006), macaca (Yang et al., 2003), cat and panda (Wen et al., 2005), human (Shi et al., 2008), and even chicken (Liu et al., 2004). However, microarray analysis failed to detect significant human genome reprogramming in human– rabbit iSCNT embryos (Chung et al., 2009). "
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ABSTRACT: Pluripotent stem cells would have great potential in cell therapies and drug development when genetically matched with the patient; thus, histocompatible cells could be used in transplantation therapy or as a source of patient-specific cells for drug testing. Pluripotent embryonic stem cells (ESCs)-generated via somatic cell nuclear transfer (SCNT) or parthenogenesis (pESC)-are potential sources of histocompatible cells and tissues for transplantation. Earlier studies used the piezoelectric microinjection (PEM) technique for nuclear transfer (NT) in mouse. No specific studies examined zona-free (ZF) NT as an alternative NT method to generate genetically matched ESCs of a nuclear donor. In this study, we compared the efficiency of nuclear transfer-derived ESC (ntESC) line establishment from ZF-NT, ZF-parthenogenetic (PGA), and ZF-fertilized embryos with that of the PEM-NT method. Different nuclei donor cells [cumulus, ESC, and mouse embryonic fibroblast (MEF)] were used and the efficiency of ntESC derivation was investigated, along with their in vitro characterization. The ZF-NT method's efficiency was higher than that of the PEM-NT using cumulus cells. When ESCs and cumulus cells were used as nuclear donor cells, they resulted in significantly higher ZF-NT-derived ntESC line establishment rates compared to MEF cells. In conclusion, the nuclear donor cell type significantly affected the efficiency of ntESC line establishment, and the ZF-NT method was efficient to establish pluripotent ntESC lines.
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ABSTRACT: Mitochondrial biogenesis and function is under dual genetic control and requires extensive interaction between biparentally inherited nuclear genes and maternally inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes' mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require it to interact with an entirely foreign nucleus that is again interacting with foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and -offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can escape the selective mechanism that targets and eliminates intraspecific sperm mitochondria in the fertilized oocyte to maintain homoplasmy. However, the factors responsible for the large intra- and interindividual differences in heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably confounded with mtDNA recombination. Considering the essential roles of mitochondria in cellular metabolism, cell signalling, and programmed cell death, future experiments will need to assess the true extent and impact of unorthodox mtDNA transmission on various aspects of SCNT success.
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ABSTRACT: Mitochondrial DNA (mtDNA) encodes key proteins associated with the process of oxidative phosphorylation. Defects to mtDNA cause severe disease phenotypes that can affect offspring survival. The aim of this review is to identify how mtDNA is replicated as it transits from the fertilized oocyte into the preimplantation embryo, the fetus and offspring. Approaches for deriving offspring and embryonic stem cells (ESCs) are analysed to determine their potential application for the prevention and treatment of mtDNA disease.
The scientific literature was investigated to determine how mtDNA is transmitted, replicated and segregated during pluripotency, differentiation and development. It was also probed to understand how the mtDNA nucleoid is regulated in somatic cells.
mtDNA replication is strictly down-regulated from the fertilized oocyte through the preimplantation embryo. At the blastocyst stage, the onset of mtDNA replication is specific to the trophectodermal cells. The inner cell mass cells restrict mtDNA replication until they receive the key signals to commit to specific cell types. However, it is necessary to determine whether somatic cells reprogrammed through somatic cell nuclear transfer, induced pluripotency or fusion to an ESC are able to regulate mtDNA replication so that they can be used for patient-specific cell therapies and to model disease.
Prevention of the transmission of mtDNA disease from one generation to the next is still restricted by our lack of understanding as to how to ensure that a donor karyoplast transferred to an enucleated oocyte is free of accompanying mutant mtDNA. Techniques still need to be developed if stem cells are to be used to treat mtDNA disease in those patients already suffering from the phenotype.
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