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

Abstract

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.

Effects of resveratrol on in vitro maturation of porcine oocytes and subsequent early embryonic development following somatic cell nuclear transfer

“…Porcine somatic cell nuclear transfer (SCNT) is a required tool for human disease modelling to study pig‐to‐human xenotransplantation and for the improvement and breeding of disease‐resistant pig strains (Nagashima & Matsunari, ; Samiec & Skrzyszowska, ). The efficiency of SCNT in pigs is affected, to the highest degree, by factors such as (a) nuclear (meiotic), epigenomic and cytoplasmic maturity of nuclear recipient oocytes (Samiec & Skrzyszowska, ; Wang et al, ; Xu, Qian, Si, Qu, & Li, ); (b) epigenetic reprogrammability of somatic cell‐inherited nuclear genome (Jin et al, , ; Samiec & Skrzyszowska, ); (c) capability of nuclear‐transferred (NT) oocytes to be artificially activated (De Macedo et al, ; Samiec & Skrzyszowska, , ); (d) intergenomic communication between nuclear and mitochondrial compartments in NT oocytes and resultant cloned embryos (Estrada et al, ; Opiela, Samiec, & Romanek, ; Samiec, , ); and (e) incidence of apoptotic cell death in nuclear donor cells and cloned embryos (Ju, Rui, Lu, Lin, & Guo, ; Lee et al, ; Samiec & Skrzyszowska, ). In this regard, oocyte maturation at the nuclear, epigenomic and cytoplasmic levels seems to play a pivotal role in determining molecular quality and suitability of nuclear recipient oocytes for SCNT procedure (Jeon et al, ; Lin, Oqani, Lee, Shin, & Jin, ).…”

Pseudophysiological transcomplementary activation of reconstructed oocytes as a highly efficient method used for producing nuclear-transferred pig embryos originating from transgenic foetal fibroblast cells

“…However, because artificially-stimulated oscillatory (pulsatile) transient increase of free Ca 2+ concentration in the ooplasm differs often considerably from the physiological pattern of activation evoked through monospermic fertilisation, it can cause incorrect donor nuclear chromatin rearrangements. In turn, the latter processes may evoke delayed or improper onset of somatic genome transcriptional activity as a result of DNA partial (incomplete) demethylation wave in preimplanted nuclear-transferred pig embryos (Kang et al 2001, Samiec 2005). On the contrary, our hypothesis is that in the cytoplasmic microenvironment of porcine reconstituted oocytes undergoing the pseudophysiological transcomplementary activation, donor cell nuclei appear to be more susceptible to initiation of proper molecular mechanism for structural remodelling of transcriptionally-repressive chromatin (i.e., constitutive and facultative heterochromatin).…”

Effect of histone deacetylase inhibitor romidepsin on thein vitrogrowth of foetal fibroblast cells and early development of porcine-cloned embryos

“…Somatic cell nuclear transfer (SCNT) is of profound significance to save endangered animals, create transgenic animals, duplicate elite livestock, and provide tools and materials for basic research in biomedical field (Sameic 2005;Samiec & Skrzyszowska 2011a, 2011b. Transgenic cloned pigs are of great importance in animal husbandry and are also regarded as an ideal model for human diseases due to these characteristics of abundant resources, high fecundity, and physiological and anatomical structure similarities to humans (Samiec & Skrzyszowska 2011a;Samiec et al 2012;Kurome et al 2013;Ma et al 2016).…”

“…However, the efficiency of pig cloning remains unsatisfactory. The low efficiency in pig cloning is mainly attributed to incomplete reprogramming of the donor cell-inherited nucleus (Jeanisch et al 2002;Sameic 2004Sameic , 2005Shi et al 2015). Previously, some drugs regulating epigenetic status of donor cell nuclear chromatin in cloned embryos, such as non-specific histone deacetylase inhibitors (HDACi) including trichostatin A (TSA) (Li et al 2008;Meng et al 2009;Samiec et al 2015), Scriptaid (Chen et al 2013), valproic acid (VPA) (Costa-Borges et al 2010;Xu et al 2012), sodium butyrate (Das et al 2010) and non-selective DNA methylation inhibitors such as 5-aza-2 0 -deoxycytidine (Diao et al 2013;Huan et al 2013) and zebularine (Xiong et al 2013) have been shown to improve cloning efficiency.…”