Dynamic CpG methylation of the KCNQ1OT1 gene during maturation of human oocytes

Khoueiry, Rita; Ibala-Rhomdane, S; Méry, Laurence; Blachère, Thierry; Jf, Guérin; Lornage, Jacqueline; Lefèvre, Annick

doi:10.1136/jmg.2008.057943

Cited by 86 publications

(58 citation statements)

References 40 publications

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“…In humans, using the short-term protocol on oocytes from stimulated women, H19 GOM was found in 2/10 MII oocyte pools (Borghol et al 2006) and at 3/34 DNA strands in MII oocyte pools . KCNQ1OT1 LOM was also observed in 5/23 and 2/37 DNA strands from IVM MII oocyte pools (Khoueiry et al 2008. This contrasts with short-term IVM MII oocytes that had normal SNRPN (three single oocytes), KCNQ1OT1 (four single oocytes), and MEG3 (GTL2) (three pools of two oocytes) methylation (Geuns et al 2003(Geuns et al , 2007a(Geuns et al , 2007b.…”

Section: In Vitro Oocyte Maturationmentioning

confidence: 55%

“…As zona pellucidae were not removed from pooled oocytes, H19 GOM may be the result of cumulus cell contamination. Following ovarian stimulation in humans, individual MI oocytes showed PEG1 LOM (2/7 oocytes) and H19 GOM (2/3 oocytes) , and in the last study, pooled MII oocytes exhibited maternal KCNQ1OT1 LOM (2/19 strands) (Khoueiry et al 2008). With respect to the human MI oocyte study, PEG1 may still be in its acquisition phase.…”

Section: Ovarian Stimulationmentioning

confidence: 99%

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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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Section: In Vitro Oocyte Maturationmentioning

confidence: 55%

Section: Ovarian Stimulationmentioning

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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“…In the female germ line, only a limited number of studies are available. In one detailed analysis, methylation at the KvDMR1 was shown to be acquired progressively during oocyte maturation and to be completed by the metaphase II stage (Khoueiry et al 2008). Similarly, the SNRPN DMR was found to be fully methylated in mature oocytes (Geuns et al 2003), suggesting a timing similar to that observed in the mouse.…”

Section: Genomic Imprinting In Germ Cellsmentioning

confidence: 90%

Genomic imprinting in germ cells: imprints are under control

Arnaud¹

2010

Reproduction

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The cis-acting regulatory sequences of imprinted gene loci, called imprinting control regions (ICRs), acquire specific imprint marks in germ cells, including DNA methylation. These epigenetic imprints ensure that imprinted genes are expressed exclusively from either the paternal or the maternal allele in offspring. The last few years have witnessed a rapid increase in studies on how and when ICRs become marked by and subsequently maintain such epigenetic modifications. These novel findings are summarised in this review, which focuses on the germline acquisition of DNA methylation imprints and particularly on the combined role of primary sequence specificity, chromatin configuration, non-histone proteins and transcriptional events.

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“…In mouse, adverse effects of superovulation on imprinted gene methylation and/or expression in oocytes, embryos, fetuses, and placentas have been described [Borghol et al, 2006;Fauque et al, 2007;Sato et al, 2007;Fortier et al, 2008;Khoueiry et al, 2008;Market-Velker et al, 2010;El Hajj et al, 2011;de Waal et al, 2012;Shi et al, 2014]. In addition, our group reported a negative impact of superovulation on the expression of mRNAs encoding the BER proteins APEX1 and POLB as well as the 5-methyl-CpG-binding domain protein MBD3 in single early mouse morula embryos.…”

mentioning

confidence: 88%

Superovulation Influences Methylation Reprogramming and Delays Onset of DNA Replication in Both Pronuclei of Mouse Zygotes

Diken¹,

Linke²,

Baumgart³

et al. 2018

Cytogenet Genome Res

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Although an essential component of assisted reproductive technologies, ovarian stimulation, or superovulation, may interfere with the epigenetic reprogramming machinery during early embryogenesis and gametogenesis. To investigate the possible impact of superovulation particularly on the methylation reprogramming process directly after fertilization, we performed immunofluorescence staining of pronuclear (PN) stage embryos with antibodies against 5mC and 5hmC. PN stage embryos obtained by superovulation displayed an increased incidence of abnormal methylation and hydroxymethylation patterns in both maternal and paternal pronuclear DNA. Subsequent single-cell RT-qPCR analyses of the Tet1, Tet2, and Tet3 genes revealed no significant expression differences between PN stage embryos from spontaneously and superovulated matings that could be causative for the abnormal methylation and hydroxymethylation patterns. To analyze the possible contribution of TET-independent replication-associated demethylation mechanisms, we then determined the 5mC and 5hmC levels of PN stage mouse embryos using immunofluorescence analyses after inhibition of DNA replication with aphidicolin. Inhibition of DNA replication had no effect on abnormal methylation and hydroxymethylation patterns that still persisted in the superovulated group. Interestingly, the onset of DNA replication, which was also analyzed in these experiments, was remarkably delayed in the superovulated group. Our findings imply an impact of superovulation on both replication-dependent and -independent or yet unknown demethylation mechanisms in PN stage mouse embryos. In addition, they reveal for the first time a negative effect of superovulation on the initiation of DNA replication in PN stage mouse embryos.

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Dynamic CpG methylation of the KCNQ1OT1 gene during maturation of human oocytes

Abstract: This observation suggests that hyperstimulation likely recruits young follicles that are unable to acquire imprint at KvDMR1 during the course of the maturing process.

Cited by 86 publications

References 40 publications

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

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

Genomic imprinting in germ cells: imprints are under control

Superovulation Influences Methylation Reprogramming and Delays Onset of DNA Replication in Both Pronuclei of Mouse Zygotes

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