The effect of mitochondrial genome on architectural remodeling and epigenetic reprogramming of donor cell nuclei in mammalian nuclear transfer-derived embryos

There are some species-specific epigenetic factors present in the oocyte cytoplasm that may contribute to nucleo-cytoplasmic incompatibilities either immediately after nuclear transfer (NT) or at later stages of development. These potential incompatibilities will affect, to some degree, the ultimate utility of NT technology. It has been demonstrated that maternally inherited mitochondrial DNA molecules (mtDNAs) accumulated in the mitochondrial reservoirs of recipient-oocyte cytosol play an important role in nuclear-ooplasmic asynchrony. This asynchrony involves the incompatibility in epigenetic modifications of somatic genome supporting the developmental program of reconstituted cybrids. It also involves incompatibility in molecular mechanisms controlling the karyokinesis and cytokinesis restriction points responsible for coordinated pseudomeiotic to mitotic cycle transition following activation of the reconstituted oocyte. Moreover, the presence of oocyte-derived mitochondrial genetic apparatus influences clonal embryo implantation. For that reason, the deleterious effect on preimplantation development of NT embryos of heterogeneous mtDNA sources arising from possible mitochondrial heteroplasmy in the reconstructed nuclear-cytoplasmic hybrids, should not be discounted. That is why, the production of nuclear transfer embryos, foetuses and offspring with precisely defined constellations of nuclear and/or mitochondrial genome can be valuable for experimentally dissecting the effects of nuclear and cytoplasmic genetic/epigenetic components as well as the intrauterine environment on embryonic, foetal, and postnatal development of cloned individuals.