In vitroculture and somatic cell nuclear transfer affect imprinting of SNRPN gene in pre- and post-implantation stages of development in cattle

Suzuki, J; Therrien, Jacinthe; Lefebvre, Réjean; Goff, A.K.; Smith, Lawrence C.

doi:10.1186/1471-213x-9-9

Cited by 83 publications

(54 citation statements)

References 30 publications

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“…12,26,[67][68][69]74). We anticipate that a more complete understanding of genomic imprinting and the role it plays in early embryo development may inform future research regarding the treatment of embryos generated using ART.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies

Isom

Stevens

et al. 2013

Physiological Genomics

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Isom SC, Stevens JR, Li R, Spollen WG, Cox L, Spate LD, Murphy CN, Prather RS. Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies. Physiol Genomics 45: 577-589, 2013. First published May 21, 2013 doi:10.1152/physiolgenomics.00094.2012.-Substantial mortality of in vitro manipulated porcine embryos is observed during peri-attachment development. Herein we describe our efforts to characterize the transcriptomes of embryonic disc (ED) and trophectoderm (TE) cells from porcine embryos derived from in vivo fertilization, in vitro fertilization (IVF), parthenogenetic oocyte activation (PA), and somatic cell nuclear transfer (SCNT) on days 10, 12, and 14 of gestation. The IVF, PA, and SCNT embryos were generated with in vitro matured oocytes and were cultured overnight in vitro before being transferred to recipient females. Sequencing of cDNA from the resulting embryonic samples was accomplished with the Genome Analyzer IIx platform from Illumina. Reads were aligned to a custom-built swine transcriptome. A generalized linear model was fit for ED and TE samples separately, accounting for embryo type, gestation day, and their interaction. Those genes with significant differences between embryo types were characterized in terms of gene ontologies and KEGG pathways. Transforming growth factor-␤ signaling was downregulated in the EDs of IVF embryos. In TE cells from IVF embryos, ubiquitin-mediated proteolysis and ErbB signaling were aberrantly regulated. Expression of genes involved in chromatin modification, gene silencing by RNA, and apoptosis was significantly disrupted in ED cells from SCNT embryos. In summary, we have used high-throughput sequencing technologies to compare gene expression profiles of various embryo types during peri-attachment development. We expect that these data will provide important insight into the root causes of (and possible opportunities for mitigation of) suboptimal development of embryos derived from assisted reproductive technologies.in vitro fertilization; parthenogenesis; somatic cell nuclear transfer; in vitro embryo production; Illumina; ART IN MOST MAMMALIAN SPECIES studied to date, only 50 -70% of successfully fertilized oocytes will give rise to live, healthy offspring (reviewed in Refs. 20,57,79). Some embryos succumb to the effects of chromosomal abnormalities or faulty uterine environments, for example. But the underlying cause behind most early embryonic mortality is still poorly understood. Such inefficiency is concerning to human fertility clinical practitioners and to animal producers in agricultural settings as well. Embryos produced by assisted reproductive technologies (ART) are generally less fit and more prone to failure than in vivo produced embryos. It has been presupposed that oocyte maturation and embryo culture systems that are inadequate to promote proper development are primarily to blame, yet the precise mechanisms that contribute to deficiencies in developmental potential in in vitr...

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Section: Discussionmentioning

confidence: 99%

Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies

Isom

Stevens

et al. 2013

Physiological Genomics

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“…This large offspring syndrome in ruminants, which is somewhat reminiscent of Beckwith-Wiedemann syndrome in humans, has been linked to aberrant methylation and expression of the imprinted IGF2R gene [Young et al, 2001]. In addition, cloned bovine embryos are often affected by aberrant methylation patterns either globally or in individual genes [Cezar et al, 2003;Niemann et al, 2010] and specifically in imprinted genes [Lucifero et al, 2006;Liu et al, 2008;Suzuki et al, 2009]. It is plausible to assume that normal conception, assisted reproduction and embryo cloning are all susceptible to similar dysregulation of epigenetic components.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development

Hansmann¹,

Heinzmann²,

Wrenzycki³

et al. 2010

Cytogenet Genome Res

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Correct imprinting is crucial for normal fetal and placental development in mammals. Experimental evidence in animal models and epidemiological studies in humans suggest that assisted reproductive technologies (ARTs) can interfere with imprinted gene regulation in gametogenesis and early embryogenesis. Bos taurus is an agriculturally important species in which ARTs are commonly employed. Because this species exhibits a similar preimplantation development and gestation length as humans, it is increasingly being used as a model for human germ-cell and embryo development. However, in contrast to humans and mice, there is relatively little information on bovine imprinted genes. Here, we characterized the bovine intergenic IGF2-H19 imprinting control region (ICR) spanning approximately 3 kb. We identified a 300-bp differentially methylated region (DMR) approximately 6 kb upstream of the H19 promoter, containing a CpG island with CTCF-binding site and high sequence similarity with the human intergenic ICR. Additional differentially methylated CpG islands lie –6 kb to –3 kb upstream of the promoter, however these are less conserved. Both classical bisulfite sequencing and bisulfite pyrosequencing demonstrated complete methylation of the IGF2-H19 ICR in sperm, complete demethylation in parthenogenetic embryos having only the female genome, and differential methylation in placental and somatic tissues. In addition, we established pyrosequencing assays for the previously reported bovine SNRPN and PEG3 DMRs. The observed methylation patterns were consistent with genomic imprinting in all analyzed tissues/cell types. The identified IGF2-H19 ICR and the developed quantitative methylation assays may prove useful for further studies on the relationship between ARTs and imprinting defects in the bovine model.

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“…ART-conceived AS patients often possess maternal SNRPN LOM. human, it is important to note that work in other animal models, such as sheep and cattle, support the studies described herein (for example, see Young et al (2001), Suzuki et al (2009), Hori et al (2010, Barboni et al (2011) and Heinzmann et al (2011)). Paramount to assisted reproduction is that timing of ARTs coincides with crucial epigenetic events during gametogenesis and early embryogenesis (Fig.…”

Section: Genomic Imprinting: a Model For Epigenetic Stabilitymentioning

confidence: 99%

Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies

Denomme¹,

Mann²

2012

Reproduction

112

118

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Gamete and early embryo development are important stages when genome-scale epigenetic transitions are orchestrated. The apparent lack of remodeling of differential imprinted DNA methylation during preimplantation development has lead to the argument that epigenetic disruption by assisted reproductive technologies (ARTs) is restricted to imprinted genes. We contend that aberrant imprinted methylation arising from assisted reproduction or infertility may be an indicator of more global epigenetic instability. Here, we review the current literature on the effects of ARTs, including ovarian stimulation, in vitro oocyte maturation, oocyte cryopreservation, IVF, ICSI, embryo culture, and infertility on genomic imprinting as a model for evaluating epigenetic stability. Undoubtedly, the relationship between impaired fertility, ARTs, and epigenetic stability is unquestionably complex. What is clear is that future studies need to be directed at determining the molecular and cellular mechanisms giving rise to epigenetic errors.

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In vitroculture and somatic cell nuclear transfer affect imprinting of SNRPN gene in pre- and post-implantation stages of development in cattle

Cited by 83 publications

References 30 publications

Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies

Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies

Characterization of Differentially Methylated Regions in 3 Bovine Imprinted Genes: A Model for Studying Human Germ-Cell and Embryo Development

Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies

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