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Abnormal methylation of KCNQ1OT1 and differential methylation of H19 imprinting control regions in human ICSI embryos

Published online by Cambridge University Press:  02 February 2012

Rita Khoueiry ,
Samira Ibala-Romdhane ,
Mohamed Al-Khtib ,
Thierry Blachère ,
Jacqueline Lornage ,
Jean-.François Guérin  and
Annick Lefèvre
Rita Khoueiry
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France.
Samira Ibala-Romdhane
Affiliation:
Service Cytogénétique et Biologie de la Reproduction, Hôpital Farhat Hached, 4000 Sousse, Tunisie.
Mohamed Al-Khtib
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France.
Thierry Blachère
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France.
Jacqueline Lornage
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France. Service de Biologie de la Reproduction, Hôpital Femme Mère Enfants, 69500 Bron, France.
Jean-.François Guérin
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France. Service de Biologie de la Reproduction, Hôpital Femme Mère Enfants, 69500 Bron, France.
Annick Lefèvre*
Affiliation:
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France. INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France.
*
All correspondence to: Annick Lefèvre. INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France. Tel: +33 4 78 77 28 79. Fax: +33 4 78 77 72 64. e-mail: [email protected]
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Summary

To evaluate the integrity of genomic imprinting in embryos that failed to develop normally following intracytoplasmic sperm injection (ICSI), we analysed the methylation profile of H19 and KCNQ1OT1 imprinting control regions, H19DMR and KvDMR1 respectively, in high-grade blastocysts and in embryos that exhibited developmental anomalies. Significant hypomethylation of KvDMR1 was specifically observed in 5/5 atypical blastocysts graded BC, which probably reflected the vulnerability of the imprint in the inner cell mass during the methylation remodelling phase in the early embryo. In addition, KvDMR1 was hypermethylated in 2/5 CC graded atypical blastocysts and in 2/8 embryos that exhibited developmental delay. H19DMR appeared differentially methylated in all groups of embryos. DNA methyltransfersase 1 (DNMT1) expression was similar in most of the tested embryos and could not account for the abnormal methylation patterns of KvDMR1 observed.

Keywords

ARTDevelopmentHuman blastocystsImprintingKCNQ1OT1
Type
Research Article
Information
Zygote , Volume 21 , Issue 2 , May 2013 , pp. 129 - 138
Copyright
Copyright © Cambridge University Press 2012

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