Assisted Reproductive Technology affects developmental kinetics, H19 Imprinting Control Region methylation and H19gene expression in individual mouse embryos

Fauque, Patricia; Jouannet, Pierre; Lesaffre, Corinne; Ripoche, Marie‐Anne; Dandolo, Luisa; Vaiman, Daniel; Jammes, Hélène

doi:10.1186/1471-213x-7-116

Cited by 189 publications

(147 citation statements)

References 67 publications

(72 reference statements)

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“…We also detected a significant reduction of paternal-specific methylation at the H19 DMR in muscle cells of one ICSI-derived male mouse that was not correlated with abnormal expression from the repressed allele in these same cells. This observation is consistent with previous reports that loss of DNA methylation at a DMR is not always associated with ectopic expression of the normally repressed allele (19,20). Importantly, none of the ICSIderived mice produced in this study exhibited any obvious morphological or functional abnormalities, and all were able to reproduce naturally.…”

Section: Discussionsupporting

confidence: 81%

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Waal

Yamazaki

Ingale

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The use of assisted reproductive technologies (ART) has become increasingly common worldwide and is now responsible for 2-3% of children born in developed countries. Multiple reports have suggested that ART-conceived children are more likely to develop rare epigenetic disorders such as Beckwith-Wiedemann Syndrome or Angelman Syndrome, both of which involve dysregulation of imprinted genes. Anecdotal reports suggest that animals produced with ART that manifest apparent epigenetic defects typically do not transmit these epimutations to subsequent generations when allowed to breed naturally, but this hypothesis has not been directly studied. We analyzed allele-specific DNA methylation and expression at three imprinted genes, H19, Snrpn, and Peg3, in somatic cells from adult mice generated with the use of intracytoplasmic sperm injection (ICSI), a type of ART. Epimutations were detected in most of the ICSI-derived mice, but not in somatic cells of their offspring produced by natural mating. We examined germ cells from the ICSI mice that exhibited epimutations in their somatic cells and confirmed normal epigenetic reprogramming of the three imprinted genes analyzed. Collectively, these results confirm that ART procedures can lead to the formation of primary epimutations, but while such epimutations are likely to be maintained indefinitely in somatic cells of the ART-derived individuals, they are normally corrected in the germ line by epigenetic reprogramming and thus, not propagated to subsequent generations.gametogenesis | transgenerational inheritance E arly embryos and germ cells are unique in that they must undergo extensive epigenetic reprogramming to reestablish developmental potency during each generation. This reprogramming entails erasure of most inherited epigenetic modifications followed by the acquisition and subsequent maintenance of new epigenetic profiles (1). Genomic imprinting is an epigenetic phenomenon found in eutherian and metatherian mammals (2) that results in parent-of-origin-specific, monoallelic expression of a subset of genes (3). This functional asymmetry of imprinted genes is conferred through differential DNA methylation patterns established during gametogenesis in each parent that distinguish the maternal and paternal alleles in the ensuing offspring (4, 5). These regions are known as differentially methylated regions (DMRs), and the differential methylation profiles at these genetic elements play an important role in regulating allele-specific expression of imprinted genes (3).Because the epigenome is distinct in each cell type and is readily reversible by developmental reprogramming, it is particularly susceptible to disruption by environmental influences (6). Such epigenetic defects are known as "epimutations" and can be of two types-primary epimutations or secondary epimutations (7). Primary epimutations result from a direct disruption of an epigenetic parameter such as DNA methylation that is then propagated through DNA replication to subsequent cells. Secondary epimutations result...

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Section: Discussionsupporting

confidence: 81%

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Waal

Yamazaki

Ingale

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been postulated that human embryos are exposed to constant stress under in vitro conditions as none of the culture media fully mimic the in vivo milieu [1]. Adaptation of embryos to stress has consequences such as diminished development due to increased cell death [2] and alterations in expression or imprinting of key genes [3,4]. Culture media has also been shown to influence development and birth-weight of the fetus [5].…”

Section: Introductionmentioning

confidence: 99%

Time-lapse evaluation of human embryo development in single versus sequential culture media—a sibling oocyte study

Ciray¹,

Aksoy²,

Göktaş³

et al. 2012

J Assist Reprod Genet

142

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Objective To compare the dynamics of early development between embryos cultured in single and sequential media. Design Randomized, comparative study. Setting Private IVF centre. Patients A total of 446 metaphase II oocytes from 51 couples who underwent oocyte retrieval procedure for intracytoplasmic sperm injection. Forty-nine resulted in embryo transfer. Intervention Oocytes were split between single and sequential media produced by the same manufacturer and cultured in a time-lapse incubator. Main outcome measures Morphokinetic parameters until the embryos reached the 5-cell stage (t5), utilization, clinical pregnancy and implantation rates. Results Embryos cultured in single media were advanced from the first mitosis cycle and reached 2-to 5-cell stages earlier. There was not any difference between the durations for cell cycle two (cc20t3-t2) and s2 (t4-t3). The utilization, clinical pregnancy and implantation rates did not differ between groups. The proportion of cryopreserved day6 embryos to two pronuclei oocytes was significantly higher in sequential than in single media. Conclusions Morphokinetics of embryo development vary between single and sequential culture media at least until the 5-cell stage. The overall clinical and embryological parameters remain similar regardless of the culture system.

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“…The effect of in vitro fertilization (IVF) on DNA methylation in mouse embryos has been demonstrated in many studies (5,(7)(8)(9). Small epidemiology studies in humans have suggested a 4-to 9-fold increased incidence of BeckwithWiedemann syndrome (BWS) among children conceived by IVF or intracytoplasmic sperm injection (ICSI) (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…Allelic expression of imprinted genes is controlled by differentially methylated regions (DMRs) which are thought to function as imprinting control centers (4). DMRs are thought to be particularly sensitive to disruption by environmental factors such as the large amounts of gonadotropin and different culture mediums (5,6).…”

Section: Introductionmentioning

confidence: 99%

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Zheng

Shi

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Assisted reproductive technology (ART) includingin vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been shown to be associated with abnormal genomic imprinting, thus increasing the incidence of imprinting disorders such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) in ART-conceived children. Furthermore, a recent study described abnormal DNA methylation in clinically normal children conceived by ART. However, data from different studies are conflicting or inconclusive. This study examined DNA methylation patterns of multiple imprinted genes in children born after ART to primarily evaluate the impact of ART on genomic imprinting. A total of 101 newborns conceived by ART (40 ICSI and 61 IVF) and 60 naturally conceived newborns were involved in our study. After obtaining the approval of the Institutional Ethics Committee, umbilical cord blood was collected from each infant. Genomic DNA was isolated from each blood sample and treated using sodium bisulfite. Subsequently, using methylation-specific PCR (MS-PCR), we analyzed six differentially methylated regions (DMRs) including KvDMR1, SNRPN, MEST, MEG3, TNDM and XIST. Meanwhile, information regarding twin pregnancies, gestational age, and birth weight of the neonates was documented. None of the cases presented with phenotypic abnormalities. Children conceived by ART were more likely to have low birth weight and to be born before term, compared with children conceived spontaneously. However, 7 months to 3 years of clinical follow-up showed that none of the children had clinical symptoms of any imprinting diseases. Furthermore, the MS-PCR results showed that all 161 children had normal DNA methylation patterns at six DMRs despite the different mode of conception. Our data did not indicate a higher risk of DNA-methylation defects in children born after ART. However, further studies using quantitative methods are needed to confirm these results.

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Assisted Reproductive Technology affects developmental kinetics, H19 Imprinting Control Region methylation and H19gene expression in individual mouse embryos

Cited by 189 publications

References 67 publications

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

Time-lapse evaluation of human embryo development in single versus sequential culture media—a sibling oocyte study

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

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