Abnormal methylation of KCNQ1OT1 and differential methylation of H19 imprinting control regions in human ICSI embryos.
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.
INSERM U846, Institut Cellule Souche et Cerveau, 18 Av Doyen Lépine, 69500 Bron, France.
Rita
R
Khoueiry
Samira
S
Ibala-Romdhane
Mohamed
M
Al-Khtib
Thierry
T
Blachère
Jacqueline
J
Lornage
Jean-François
JF
Guérin
Annick
A
Lefèvre
D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020554:Sperm Injections, Intracytoplasmic
C094335:H19 long non-coding RNA; C449939:KCNQ1OT1 RNA; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human