The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development
Abstract
In vitro culture of mouse embryos results in loss of imprinting. The aim of the present study was to examine how two of the techniques commonly used during assisted reproduction, namely embryo culture and embryo transfer, affect genomic imprinting after implantation in the mouse. F1 hybrid mouse embryos were subjected to three experimental conditions: control (unmanipulated), embryo transfer and in-vitro-culture followed by embryo transfer. Concepti were collected on d9.5 of development and allelic expression determination of ten imprinted genes (H19, Snrpn, Igf2, Kcnq1ot1, Cdkn1c, Kcnq1, Mknr3, Ascl2, Zim1, Peg3) was performed. Although control concepti had monoallelic imprinted gene expression in all tissues, both manipulated groups had aberrant expression of one or more imprinted genes in the yolk sac and placenta. Culture further exacerbated the effects of transfer by increasing the number of genes with aberrant allelic expression in extraembryonic, as well as embryonic tissues. Additionally, placentae of both groups of manipulated concepti exhibited reduced levels of Igf2 mRNA and increased levels of Ascl2 mRNA when compared with their unmanipulated counterparts. Furthermore, we show that biallelic expression of Kcnq1ot1 coincided with loss of methylation on the maternal allele of the KvDMR1 locus, a phenotype often associated with the human syndrome Beckwith-Wiedemann. In conclusion, our results show that even the most basic manipulation used during human-assisted reproduction, namely, embryo transfer, can lead to misexpression of several imprinted genes during post-implantation development. Additionally, our results serve as a cautionary tale for gene expression studies in which embryo transfer is used.
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Cites
Parental imprinting of the mouse insulin-like growth factor II gene
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Placental-specific IGF-II is a major modulator of placental and fetal growth
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Differential Effects of Culture on Imprinted H19 Expression in the Preimplantation Mouse Embryo1
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Self-citationIntracytoplasmic Sperm Injection May Increase the Risk of Imprinting Defects
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A census of mammalian imprinting
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Beckwith-Wiedemann syndrome and assisted reproduction technology (ART): Table 1
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Cited by
Origins of lifetime health around the time of conception: causes and consequences
Fleming, T. P., Watkins, A. J., Velazquez, M. A., Mathers, J. C., Prentice, A. M., Stephenson, J., Barker, M., Saffery, R., Yajnik, C. S., Eckert, J. J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30312-x · Cited by 1,147
Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy
Mueller, B. R., & Bale, T. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1424-08.2008 · Cited by 988
X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease
Lee, J. T., & Bartolomei, M. S. (2013) · Cell · doi:10.1016/j.cell.2013.02.016 · Cited by 676
Self-citationDNA methylation and gene expression differences in children conceived in vitro or in vivo
Katari, S., Turan, N., Bibikova, M., Erinle, O., Chalian, R., Foster, M., Gaughan, J. P., Coutifaris, C., & Sapienza, C. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp319 · Cited by 470
Nelissen, E. C. M., van Montfoort, A. P. A., Dumoulin, J. C. M., & Evers, J. L. H. (2011) · Human Reproduction Update · doi:10.1093/humupd/dmq052 · Cited by 384
Metadata
- Authors
- Rivera, R. M., Stein, P., Weaver, J. R., Mager, J., Schultz, R. M., & Bartolomei, M. S.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-09-27
- Volume
- 17
- Issue
- 1
- Pages
- 1-14
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2114100575
- Cited by
- 324
- References
- 63
- FWCI
- 11.89
- Type
- journal article
- Language
- en
- Open access
- closed
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- Rivera, R. M., Stein, P., Weaver, J. R., Mager, J., Schultz, R. M., & Bartolomei, M. S. (2008). Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddm280
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