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PMID: 19471309 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm.

European journal of human genetics : EJHG ·Vol. 17 ·No. 12 ·2009-12-00 ·Pages 1582-91

Kobayashi H, Hiura H, John RM, Sato A, Otsu E, Kobayashi N, Suzuki R, Suzuki F, Hayashi C, Utsunomiya T, Yaegashi N, Arima T

Abstract

There is an increased prevalence of imprinting disorders, such as Beckwith-Wiedemann syndrome, associated with human assisted reproductive technologies (ART). Work on animal models suggests that in vitro culture may be the source of these imprinting errors. However, in this study we report that, in some cases, the errors are inherited from the father. We analyzed DNA methylation at seven autosomal imprinted loci and the XIST locus in 78 paired DNA samples. In seven out of seventeen cases where there was abnormal DNA methylation in the ART sample (41%), the identical alterations were present in the parental sperm. Furthermore, we also identified DNA sequence variations in the gene encoding DNMT3L, which were associated with the abnormal paternal DNA methylation. Both the imprinting errors and the DNA sequence variants were more prevalent in patients with oligospermia. Our data suggest that the increase in the incidence of imprinting disorders in individuals born by ART may be due, in some cases, to the use of sperm with intrinsic imprinting mutations.

MeSH Terms
DNA (Cytosine-5-)-Methyltransferases/genetics DNA Methylation/genetics DNA Methyltransferase 3A DNA Mutational Analysis Embryo, Mammalian/metabolism Genetic Loci/genetics Genomic Imprinting/genetics Humans Infertility, Male/enzymology,genetics Male Mutation/genetics Parents Polymerase Chain Reaction Reproductive Techniques, Assisted Spermatozoa/enzymology,metabolism
Chemicals
DNMT3A protein, human DNMT3L protein, human DNA (Cytosine-5-)-Methyltransferases DNA Methyltransferase 3A
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Kobayashi Hisato
Innovation of New Biomedical Engineering Center, Tohoku University Graduate School of Medicine, Sendai, Japan.
Hiura Hitoshi
John Rosalind M
Sato Akiko
Otsu Eiko
Kobayashi Naoko
Suzuki Rei
Suzuki Fumihiko
Hayashi Chika
Utsunomiya Takafumi
Yaegashi Nobuo
Arima Takahiro
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34 references, click to expand
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Article Info
Journal
European journal of human genetics : EJHG
Abbr.
Eur J Hum Genet
ISSN
1476-5438
DOI
10.1038/ejhg.2009.68
Published
2009-12-00
Epub
2009-00-27
Pages
1582-91
Language
English
Region
England
NLM ID
9302235
PMCID
PMC2845511
Subset
IM
External Links
PubMed source DOI: 10.1038/ejhg.2009.68 PMC Full Text View journal details
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