Selective loss of imprinting in the placenta following preimplantation development in culture

Mann, Mellissa R.W.; Lee, Susan S.; Doherty, Adam S.; Verona, Raluca; Nolen, Leisha D.; Schultz, Richard M.; Bartolomei, Marisa S.

doi:10.1242/dev.01241

Cited by 403 publications

(354 citation statements)

References 49 publications

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“…In this study, the in vivo-produced blastocysts were different from the other blastocysts in that there was no time in culture. For example, previous studies have shown that epigenetic changes caused by in vitro preimplantation culture results in aberrant methylation and expression of a number of imprinted genes (Sasaki et al, 1995;Doherty et al, 2000;Mann et al, 2004). Further, the authors suggest that the epigenetic remodeling and reprogramming of the trophoblast may be more sensitive to the disruptive effect of the culture media than the ICM.…”

Section: Discussionmentioning

confidence: 99%

Aberrant DNA methylation in porcine in vitro‐, parthenogenetic‐, and somatic cell nuclear transfer‐produced blastocysts

Bonk

Lai

et al. 2007

Molecular Reproduction Devel

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Early embryonic development in the pig requires DNA methylation remodeling of the maternal and paternal genomes. Aberrant remodeling, which can be exasperated by in vitro technologies, is detrimental to development and can result in physiological and anatomic abnormalities in the developing fetus and offspring. Here, we developed and validated a microarray based approach to characterize on a global scale the CpG methylation profiles of porcine gametes and blastocyst stage embryos. The relative methylation in the gamete and blastocyst samples showed that 18.5% (921/4,992) of the DNA clones were found to be significantly different (P < 0.01) in at least one of the samples. Furthermore, for the different blastocyst groups, the methylation profile of the in vitro-produced blastocysts was less similar to the in vivo-produced blastocysts as compared to the parthenogenetic-and somatic cell nuclear transfer (SCNT)-produced blastocysts. The microarray results were validated by using bisulfite sequencing for 12 of the genomic regions in liver, sperm, and in vivoproduced blastocysts. These results suggest that a generalized change in global methylation is not responsible for the low developmental potential of blastocysts produced by using in vitro techniques. Instead, the appropriate methylation of a relatively small number of genomic regions in the early embryo may enable early development to occur. Mol. Reprod.

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Section: Discussionmentioning

confidence: 99%

Aberrant DNA methylation in porcine in vitro‐, parthenogenetic‐, and somatic cell nuclear transfer‐produced blastocysts

Bonk

Lai

et al. 2007

Molecular Reproduction Devel

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“…In case of the BiCHMs, the labile nature of maternal imprints in placental tissues during early development may explain the loss of maternal imprints. 22 Finally, the abnormal methylation patterns on the maternal alleles of maternally or paternally expressed genes in biparental molar tissues may have not occurred at all DMRs at the same time, but resulted from several events that altogether led to the molar phenotype. …”

Section: Discussionmentioning

confidence: 99%

Patients with familial biparental hydatidiform moles have normal methylation at imprinted genes

El‐Maarri¹,

Seoud

Rivière

et al. 2005

Eur J Hum Genet

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In molar tissues from patients with recurrent biparental hydatidiform moles, we could previously demonstrate that differentially methylated regions (DMRs) of four imprinted genes are abnormally methylated on the maternal alleles. It remained unclear if this abnormal methylation originated de novo in the molar tissues or if it is even recognizable in the patient somatic tissues. To address this question, we investigated the DNA methylation of four imprinted genes in total blood from the two sister-patients. Here, we show that both patients retain normal methylation levels at the DMRs of the four genes in blood tissues. For two maternally expressed genes, we could use informative SNPs to follow the inheritance of the abnormally methylated maternal alleles in the molar tissues. We find that the transmitted abnormally methylated maternal alleles to the moles originated from the maternal grandmother and that the same alleles are not methylated in the patients. Our data suggest that the abnormal methylation in familial biparental molar tissues was acquired de novo in the patients'germline as a result of a false reprogramming or during the postzygotic development of the conceptuses that led to moles.

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“…First, in vitro culture may impinge on the imprinting process of IVF blastocysts. This hypothesis is supported by recent evidence that murine H19 imprinting is lost in embryos following culture in Whitten's medium and that this loss of imprinting persists in mid-gestation conceptuses (Doherty et al 2000;Mann et al 2004). However, the fact that approximately 60% of IVF blastocysts, when compared with in vivo embryo transfers, result in live births suggests that the effects of in vitro culture may not explain fully the results obtained (Peterson and Lee 2003).…”

Section: Genomic Imprinting Statusmentioning

confidence: 93%

Putative imprinted gene expression in uniparental bovine embryo models

Cruz

Wilson

Cooney

et al. 2008

Reprod. Fertil. Dev.

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Abstract. Altered patterns of gene expression and the imprinted status of genes have a profound effect on cell physiology and can markedly alter embryonic and fetal development. Failure to maintain correct imprinting patterns can lead to abnormal growth and behavioural problems, or to early pregnancy loss. Recently, it has been reported that the Igf2R and Grb10 genes are biallelically expressed in sheep blastocysts, but monoallelically expressed at Day 21 of development. The present study investigated the imprinting status of 17 genes in in vivo, parthenogenetic and androgenetic bovine blastocysts in order to determine the prevalence of this unique phenomenon. Specifically, the putatively imprinted genes Ata3, Impact, L3Mbtl, Magel2, Mkrn3, Peg3, Snrpn, Ube3a and Zac1 were investigated for the first time in bovine in vitro fertilised embryos. Ata3 was the only gene not detected. The results of the present study revealed that all genes, except Xist, failed to display monoallelic expression patterns in bovine embryos and support recent results reported for ovine embryos. Collectively, the data suggest that monoallelic expression may not be required for most imprinted genes during preimplantation development, especially in ruminants. The research also suggests that monoallelic expression of genes may develop in a gene-and time-dependent manner.

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Selective loss of imprinting in the placenta following preimplantation development in culture

Cited by 403 publications

References 49 publications

Aberrant DNA methylation in porcine in vitro‐, parthenogenetic‐, and somatic cell nuclear transfer‐produced blastocysts

Aberrant DNA methylation in porcine in vitro‐, parthenogenetic‐, and somatic cell nuclear transfer‐produced blastocysts

Patients with familial biparental hydatidiform moles have normal methylation at imprinted genes

Putative imprinted gene expression in uniparental bovine embryo models

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