Aberrant methylation patterns at the two‐cell stage as an indicator of early developmental failure

Wei, Shi; Haaf, Thomas

doi:10.1002/mrd.90016

Cited by 234 publications

(155 citation statements)

References 35 publications

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“…Epigenetic abnormalities of ES cells are not corrected in differentiated tissue derivatives (30), and the epigenetic status of the embryo used to derive ES cells may influence the developmental potential of the ES cells obtained. Additionally, in vitro fertilization, embryo culture, nuclear transfer, and superovulation are known to cause methylation defects that can result in abnormal development (31,32), and further consideration must be afforded to how these manipulations are affecting the normalcy of resulting ES cell lines, especially in the human. The paucity of human embryos available for research and the lack of an analogous chimera assay impede rigorous characterization of the normal developmental potential of hES cells.…”

Section: Discussionmentioning

confidence: 99%

Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos

Tesar

2005

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos

Tesar

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Studies evaluating DNA methylation patterns in developing NT embryos indicate that demethylation and remethylation events are not always faithfully recapitulated in the mouse (Shi & Haaf 2002, Mann et al 2003) and the cow (Bourc'his et al 2001, Dean et al 2001, Kang et al 2002. It is also clear that histone acetylation is sometimes aberrant in bovine NT embryos (Santos et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Effect of the time interval between fusion and activation on nuclear state and development in vitro and in vivo of bovine somatic cell nuclear transfer embryos

Aston¹,

Li²,

Hicks³

et al. 2006

Reproduction

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This study indicated that prolonged exposure of donor cell nuclei to oocyte cytoplasm before activation results in abnormal chromatin morphology, and reduced development to compacted morula/blastocyst stage in vitro. However, after transfer of embryos to recipients, there was no difference in pregnancy rates throughout gestation. Chromatin morphology was evaluated for embryos held 2, 3, 4 and 5 h between fusion and activation. In embryos held 2 h, 15/17 (88.2%) embryos contained condensed chromosomes, while only 12/24 (50.0%) embryos held 3 h exhibited this characteristic. The proportion of embryos with elongated or fragmented chromosomes tended to increase with increased hold time. While 15/19 (78.9%) of embryos held 2 h developed a single pronucleus 6 h after activation, only 8/22 (36.4%) had one pronucleus after a 4-h hold. Embryos held 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 h cleaved at rates of 207/281 (73.7%), 142/166 (85.5%), 655/912 (71.8%), 212/368 (57.6%), 406/667 (60.9%), 362/644 (56.2%) and 120/228 (52.6%) respectively. Further development to compacted morula/blastocyst stage occurred at rates of 78/281 (27.8%), 42/166 (25.3%), 264/912 (28.9%), 79/368 (21.5%), 99/667 (14.8%), 94/644 (14.6%) and 27/228 (11.8%) respectively. Embryos held less than 2.5 h between fusion and activation established pregnancies in 18/66 (27.3%) of recipients, while embryos held over 2.5 h established pregnancies at a rate of 17/57 (29.8%). This study indicates that holding bovine nuclear transfer embryos less than 2.5 h between fusion and activation results in improved nuclear morphology and increased development to compacted morula/blastocyst stage, and results in pregnancy rates equivalent to embryos held over 2.5 h.

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“…These changes are associated with both early developmental failure (35,45) or serious phenotypic defects (reviewed in refs. 46 and 47).…”

Section: Function Of Pronuclear Demethylation?mentioning

confidence: 99%

The effect of interspecific oocytes on demethylation of sperm DNA

Beaujean

Taylor

McGarry

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

114

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In contrast to mice, in sheep no genome-wide demethylation of the paternal genome occurs within the first postfertilization cell cycle. This difference could be due either to an absence of a sheep demethylase activity that is present in mouse ooplasm or to an increased protection of methylated cytosine residues in sheep sperm. Here, we use interspecies intracytoplasmic sperm injection to demonstrate that sheep sperm DNA can be demethylated in mouse oocytes. Surprisingly, mouse sperm can also be demethylated to a limited extent in sheep oocytes. Our results suggest that the murine demethylation process is facilitated either by a spermderived factor or by male pronuclear chromatin composition.M ethylation of the DNA cytosine residues in CpG dinucleotides is part of the complex epigenetic mechanism that has evolved to silence genomic sequences where their transcription either is not required for development or may be detrimental to genomic stability (reviewed in refs. 1-3). DNA methylation also plays an important role in allele-specific repression at imprinted gene loci, regulating such processes as fetal growth and development as well as X inactivation (reviewed in refs. 4-6). Whereas the genome-wide methylation patterns and levels of differentiated somatic lineages remain largely constant, very dynamic changes have been reported to occur in the preimplantation embryo in association with the formation of pluripotent embryonic nuclei.After fertilization, the sperm and egg genomes are remodeled into pronuclei, which appose within the oocyte cytoplasm before the first embryonic mitosis. However, the highly condensed sperm chromatin requires extensive nuclear remodeling and protamine-histone exchange, unlike nucleosomal maternal chromatin. By using an antibody against 5-methylcytosine (5mC), the presumptive male pronucleus of mouse, rat, pig, human, and, to a lesser extent, cow embryos have been shown to actively demethylate before syngamy, whereas the female pronucleus retains genome-wide methylation (7-12). In contrast, active demethylation of the paternal genome is not observed in early sheep or rabbit embryos (with an intermediate state in the cow) (12), which suggests that it is not an obligate requirement for mammalian development. The discovery that the dramatic changes in DNA methylation associated with early formative events in the mouse embryo are not conserved in the sheep allows a unique opportunity to investigate the regulatory mechanisms involved. Mouse ooplasm can fully demethylate multiple male pronuclei in polyspermic embryos, which raises the question of whether the demethylating activity resides in the fertilized oocyte or is intimately associated with the sperm (10). We have now used interspecies intracytoplasmic sperm injection (ICSI) to mimic the events of normal fertilization and investigate whether species differences in the oocyte environment or sperm composition determines the extent of male pronuclear demethylation. Materials and MethodsAll animal procedures were under strict accordance with...

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Aberrant methylation patterns at the two‐cell stage as an indicator of early developmental failure

Cited by 234 publications

References 35 publications

Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos

Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos

Effect of the time interval between fusion and activation on nuclear state and development in vitro and in vivo of bovine somatic cell nuclear transfer embryos

The effect of interspecific oocytes on demethylation of sperm DNA

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