Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction

Hajj, Nady El; Haaf, Thomas

doi:10.1016/j.fertnstert.2012.12.044

Cited by 176 publications

(125 citation statements)

References 134 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Animal models have confirmed that techniques used in ART can cause epigenetic perturbations at imprinted (and other) loci (El Hajj and Haaf, 2013, Grace and Sinclair, 2009, Laprise, 2009. The animal models have the added attraction that infertility is not a confounding factor.…”

Section: Assisted Reproductive Technologies and Imprinting Disordersmentioning

confidence: 87%

Epigenetics and imprinting in human disease

Jiang²,

2014

View full text Add to dashboard Cite

Most genes are expressed from both parental chromosomes; however, a small number of genes in mammals are imprinted and expressed in a parent-of-origin specific manner. These imprinted genes play an important role in embryonic and extraembryonic growth and development, as well as in a variety of processes after birth. Many imprinted genes are clustered in the genome with the establishment and maintenance of imprinted gene expression governed by complex epigenetic mechanisms. Dysregulation of these epigenetic mechanisms as well as genomic mutations at imprinted gene clusters can lead to human disease.

show abstract

Section: Assisted Reproductive Technologies and Imprinting Disordersmentioning

confidence: 87%

Epigenetics and imprinting in human disease

Jiang²,

2014

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

“…A balanced expression of imprinted genes is indeed essential for normal embryo development, placental differentiation and pre-and postnatal growth, but also for normal neurobehavioral processes and metabolism [2,20]. Data from mouse experiments and the in vitro production of livestock provide strong evidence that imprint establishment in late oocyte stages and reprogramming of the two germline genomes for somatic development after fertilization are vulnerable to environmental cues [20]. During early life, an organism is able to adjust its phenotypic development in response to environmental cues.…”

Section: Discussionmentioning

confidence: 99%

The long-term effects of superovulation on fertility and sexual behavior of male offspring in mice

Wei

Zhang

et al. 2014

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose To evaluate the long-term effects of superovulation on fertility and sexual behavior of male offspring in mice. Method The mice were superovaluted, and the fertility of male offspring (F1 generation and F2 generation) were evaluated in terms of the percentage of plugs and pregnancies, serum testosterone concentrations, and sperm motility. Furthermore, the sexual behavior of male offspring and sex ratio (F1 generation and F2 generation) were measured. Results There were no significant differences in the percentage of plug and pregnancies, serum testosterone concentrations, sperm motilities and sex ratio between the offspring in naturally conceived group and superovulation groups (both F1 generation and F2 generation). The sperm hyperactivity at 90 min after incubation of F1 generation in naturally conceived group were higher than that of F1 generation in superovulation group, but the differences did not reach statistical significance. The offspring produced by superovaluted oocytes (both F1 generation and F2 generation) did not exhibit significant alterations in sexual behavior. Conclusions No significant alterations were found in fertility and sexual behavior of male offspring in mice produced by superovaluted oocytes compared with those of naturally conceived offspring.

show abstract

Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction

Cited by 176 publications

References 134 publications

Epigenetics and imprinting in human disease

Epigenetics and imprinting in human disease

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

The long-term effects of superovulation on fertility and sexual behavior of male offspring in mice

Contact Info

Product

Resources

About