Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer

Hall, Vanessa Jane; Compton, Duane A.; Stojković, Petra; Nesbitt, M; Herbert, Mary; Murdoch, Alison; Stojković, Miodrag

doi:10.1093/humrep/del345

Cited by 80 publications

(55 citation statements)

References 52 publications

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“…We were surprised in our threshold-based analysis ( Table 1) that, except for BUB1, the culprits of oocyte ageing were missing, such as BCL2 and BAX (mitochondrial function and apoptosis; Tatone et al 2006), APACD, SOD1, TXN1 (oxidative stress; Hamatani et al 2004, Steuerwald et al 2007), MAD2L1 (SAC; Steuerwald et al 2007, Grondahl et al 2010, ATRX, BRCA1, NUMA1, SMC1B (spindle assembly and chromosome integrity/stability; Hodges et al 2005, Hall et al 2007, Pan et al 2008, and DMAP1, DNMT1, DNMT3A, HDAC1/2 (epigenetic modification; , Pan et al 2008. Therefore, we searched for them directly, disregarding the fourfold threshold.…”

Section: Proteins Of Known Candidate Genes In the Ageing Oocyte Proteomementioning

confidence: 88%

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Schwarzer¹,

Siatkowski²,

Pfeiffer³

et al. 2014

Reproduction

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The long-standing view of 'immortal germline vs mortal soma' poses a fundamental question in biology concerning how oocytes age in molecular terms. A mainstream hypothesis is that maternal ageing of oocytes has its roots in gene transcription. Investigating the proteins resulting from mRNA translation would reveal how far the levels of functionally available proteins correlate with mRNAs and would offer novel insights into the changes oocytes undergo during maternal ageing. Gene ontology (GO) semantic analysis revealed a high similarity of the detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although not all proteins had a cognate mRNA. Concerning their dynamics, fourfold changes of abundance were more frequent in the proteome (3%) than the transcriptome (0.05%), with no correlation. Whereas proteins associated with the nucleus (e.g. structural maintenance of chromosomes and spindle-assembly checkpoints) were largely represented among those that change in oocytes during maternal ageing; proteins associated with oxidative stress/damage (e.g. superoxide dismutase) were infrequent. These quantitative alterations are either impoverishing or enriching. Using GO analysis, these alterations do not relate in any simple way to the classic signature of ageing known from somatic tissues. Given the lack of correlation, we conclude that proteome analysis of mouse oocytes may not be surrogated with transcriptome analysis. Furthermore, we conclude that the classic features of ageing may not be transposed from somatic tissues to oocytes in a one-to-one fashion. Overall, there is more to the maternal ageing of oocytes than mere cellular deterioration exemplified by the notorious increase of meiotic aneuploidy.

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Section: Proteins Of Known Candidate Genes In the Ageing Oocyte Proteomementioning

confidence: 88%

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Schwarzer¹,

Siatkowski²,

Pfeiffer³

et al. 2014

Reproduction

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“…The scarcity of donated mature human metaphase II oocytes available for research is a significant impediment. Using an alternative source of failed-to-fertilize human oocytes obtained at 16 -18 hours postinsemination [19] or 48 hours after retrieval [20] resulted in cleavage abnormalities and early-embryonic arrest, primarily as a consequence of aneuploidy and spindle defects. These types of oocytes also appear to be more difficult to enucleate and fuse compared with freshly recovered human oocytes [20].…”

Section: Introductionmentioning

confidence: 99%

“…Using an alternative source of failed-to-fertilize human oocytes obtained at 16 -18 hours postinsemination [19] or 48 hours after retrieval [20] resulted in cleavage abnormalities and early-embryonic arrest, primarily as a consequence of aneuploidy and spindle defects. These types of oocytes also appear to be more difficult to enucleate and fuse compared with freshly recovered human oocytes [20]. The use of aged oocytes has been reported to support embryonic nuclear remodeling and reprogramming to various degrees in the rabbit [21], mouse [22], and bovine [23].…”

Section: Introductionmentioning

confidence: 99%

Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts

French¹,

et al. 2008

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Nuclear transfer stem cells hold considerable promise in the field of regenerative medicine and cell-based drug discovery. In this study, a total of 29 oocytes were obtained from three young (20 -24 years old) reproductive egg donors who had been successful in previous cycles. These oocytes, deemed by intended parents to be in excess of their reproductive needs, were donated for research without financial compensation by both the egg donor and intended parents after receiving informed consent. All intended parents successfully achieved ongoing pregnancies with the oocytes retained for reproductive purposes. Mature oocytes, obtained within 2 hours following transvaginal aspiration, were enucleated using one of two methods, extrusion or aspiration, after 45 minutes of incubation in cytochalasin B. Rates of oocyte lysis or degeneration did not differ between the two methods. Somatic cell nuclear transfer (SCNT) embryos were constructed using two established adult male fibroblast lines of normal karyotype. High rates of pronuclear formation (66%), early cleavage (47%), and blastocyst (23%) development were observed following incubation in standard in vitro fertilization culture media. One cloned blastocyst was confirmed by DNA and mitochondrial DNA fingerprinting analyses, and DNA fingerprinting of two other cloned blastocysts indicated that they were also generated by SCNT. Blastocysts were also obtained from a limited number of parthenogenetically activated oocytes. This study demonstrates, for the first time, that SCNT can produce human blastocyst-stage embryos using nuclei obtained from differentiated adult cells and provides new information on methods that may be needed for a higher level of efficiency for human nuclear transfer. STEM CELLS 2008;26:485-493 Disclosure of potential conflicts of interest is found at the end of this article.

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“…It is difficult to draw firm conclusions from these papers. In general, embryos produced by NT underwent few cleavage divisions and only exceptionally reached the blastocyst stage [21][22][23][24]. It must be noted, however, that cytoplasts were sourced from oocytes that were either immature at the time of egg retrieval and were subsequently in vitro matured to metaphase II stage in culture, or from oocytes deemed unsuitable for IVF.…”

Section: Inconsistent Resultsmentioning

confidence: 99%

The ups and downs of somatic cell nucleus transfer (SCNT) in humans

Fulka

Langerova

Loi

et al. 2013

J Assist Reprod Genet

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Achieving successful somatic cell nuclear transfer (SCNT) in the human and subhuman primate relative to other mammals has been questioned for a variety of technical and logistical issues. Here we summarize the gradual evolution of SCNT technology from the perspective of oocyte quality and cell cycle status that has recently led to the demonstration of feasibility in the human for deriving chromosomally normal stem cells lines. With these advances in hand, prospects for therapeutic cloning must be entertained in a conscientious, rigorous, and timely fashion before broad spectrum clinical applications are undertaken.Keywords Nucleus . Oocyte . Nucleus transfer Simply stated, SCNT in mammals should in practice be a very straightforward technique. First, cytoplasts are prepared by enucleating the metaphase II stage oocytes, i.e. metaphase II chromosomes are removed from the oocyte. Second, the selected nucleus is introduced into the cytoplast either by direct injection or by induced cell fusion. The reconstructed SCNT products are then activated in ways mimicking fertilization and if everything goes well cloned embryos develop [6].Logically, since following the birth of Dolly [7], and the production of additional clones in other mammalian species, there is ample confirmation that Dolly was not an exceptional case, prompting widespread discussion regarding the pros and cons of human SCNT. Given this prospect, it has been commonly accepted and broadly emphasized that the production of cloned human individuals must be banned (reproductive cloning). On the other hand, the production of embryos from which patient compatible embryonic stem cells could be obtained seemed to be acceptable, at least in some countries (therapeutic cloning). However, once the discovery of induced pluripotent stem cell production (iPSC) was realized by the work of Takahashi and Yamanaka [see 8 for review], illustrating that differentiated or even terminally differentiated cells can be converted (dedifferentiated) into a pluripotent state by induced overexpression of four factors (Oct 4, Sox 2, Klf 4, c-Myc; OSKM), greater resistance against the use of SCNT in humans has emerged, including the prospect of therapeutic cloning.Although many papers on modifications of the original iPS technology seeking improved efficiency and safety have been published, it should be emphasized that our understanding of the mechanisms by which iPSC elicits dedifferentiation remain woefully incomplete. Instead, it is commonly accepted that the oocyte cytoplasmic milieu is the most direct means to obtaining reprogramming of a differentiated somatic cell nucleus [9,10]. This fact-the quality of the oocyte cytoplasmic milieu-may well underscore the reason that while research on human SCNT continues, reports are rare in this species relative to the many papers published in other mammals. Birth of DollyThe work that led to the birth of Dolly was antedated by many years of experiments using laboratory and domestic animals to test many methodological combinations ...

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Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer

Abstract: Thus, aneuploidy and spindle defects may contribute to poor parthenogenetic development and developmental outcomes following NT.

Cited by 80 publications

References 52 publications

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts

The ups and downs of somatic cell nucleus transfer (SCNT) in humans

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