DNA methylation at H19/IGF2 ICR1 in the placenta of pregnancies conceived by in vitro fertilization and intracytoplasmic sperm injection

Wong, Edgar Chan; Hatakeyama, C.; Robinson, Wendy P.; Ma, Sai

doi:10.1016/j.fertnstert.2011.05.047

Cited by 39 publications

(11 citation statements)

References 28 publications

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“…Interestingly, data in support for such a genome-wide abnormality of DNA methylation in ART pregnancies is scarce, 18,20 as most available studies have focused on specific loci related to imprinted genes. [12][13][14][15][16][17][18][19] Katari et al, 20 using a custom-designed methylation array platform that examined methylation differences in placenta and cord blood samples from ART (N D 10) and naturally conceived (N D 13) pregnancies. The authors analyzed a total of 1,536 CpG sites, most of which were located in the promoters of 736 selected genes.…”

Section: Discussionmentioning

confidence: 99%

“…While some of these studies found that ART is associated with abnormal DNA methylation in human gametes, embryos, [12][13][14] placentas, 15 and umbilical cord samples, 16 other studies concluded that this association is not significant. [17][18][19] These apparently conflicting data may be attributed, at least in part, to methodological limitations of some of these studies, such as the inclusion of mixed populations in the study group (e.g., ovulation induction, IVF, and ICSI) and lack of information regarding potential confounders (e.g., indication for ART, treatment protocol, use of cleavage stage embryos vs. blastocysts, and use of frozen vs. fresh embryos). In addition, in almost all of these studies, the analysis was limited to only a small number of methylation sites.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

et al. 2015

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Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N D 10) and control pregnancies (N D 8) using a genome-wide approach with the Illumina Ò Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

et al. 2015

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“…In another study, higher PEG1 methylation levels were found in 35 IVF-conceived compared to 77 ICSI-conceived and 73 spontaneously conceived children, although no differences in mean methylation levels were identified at nine other imprinted genes (Tierling et al 2010). By comparison, normal imprinted methylation was detected at H19, KCNQ1OT1, and SNRPN in 34 IVF-and 32 ICSI-conceived children (Oliver et al 2012); at SNRPN in 92 ICSI children (Manning et al 2000); and at SNRPN in 32 IVF and 45 ICSI placentas from newborns (Wong et al 2011). While these later studies argue that the absolute risk of imprinting disorders in ARTsconceived children is small, it should be noted that many of these studies were performed on buccal and peripheral blood samples by methods that detect 1 or 2 CpGs per gene.…”

Section: Ivf and Icsimentioning

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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“…The most common region that has been examined is the IGF2 / H19 imprinting region. In placenta tissue, two studies have indicated a potential difference in methylation and expression in H19 and IGF2 [33] and expression only in H19 but not IGF2 [30] while another study found no difference in methylation [34]. Two studies examined possible difference in this region in miscarriages, abortions, and stillbirths with one finding a possible difference but more extreme values in the control group [35] and the other finding six cases with hypomethylation in the ART group and none in the control group [27].…”

Section: Discussionmentioning

confidence: 99%

“…Results have been mixed and difficult to synthesize due to differences in gene regions, tissues examined, and ways of assessing DNA methylation. However, some studies have indicated a difference in DNA methylation or gene expression in the various gene regions [24,26,27,30,32,33], although other studies have not observed a difference [25,28,29,31,34-37]. …”

Section: Introductionmentioning

confidence: 99%

Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study

et al. 2012

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BackgroundWhile a possible link between assisted reproductive technology (ART) and rare imprinting disorders has been found, it is not clear if this is indicative of subtler disruptions of epigenetic mechanisms. Results from previous studies have been mixed, but some methylation differences have been observed.MethodsChildren conceived through ART and children conceived spontaneously were recruited for this cross-sectional study. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed on five loci using pyrosequencing. Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Results are reported as differences with 95% confidence intervals (CI).ResultsA total of 67 ART children and 31 spontaneously conceived (SC) children participated. No significant difference in methylation in lymphocyte samples was observed between groups for any loci. Possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.07; 95% confidence interval (CI): -0.28, 4.42; p = 0.08) and IGF2R (Difference: -2.79; 95% CI: -5.74, 0.16; p = 0.06). Subgroup analysis indicated potential lower methylation in those whose parents used ART for unexplained infertility.ConclusionsObserved differences in methylation between the ART and SC groups were small for all loci in the two sample types examined and no statistical differences were observed. It is still unclear whether or not small differences observed in several studies represent a real difference between groups and if this difference is biologically meaningful. Larger studies with long term follow-up are needed to fully answer these questions.

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DNA methylation at H19/IGF2 ICR1 in the placenta of pregnancies conceived by in vitro fertilization and intracytoplasmic sperm injection

Cited by 39 publications

References 28 publications

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

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

Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study

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