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

Hisato Kobayashi, Hitoshi Hiura, Rosalind M. John, Akiko Sato, Eiko Otsu, Naoko Kobayashi, Rei Suzuki, Fumihiko Suzuki, Chika Hayashi, Takafumi Utsunomiya, Nobuo Yaegashi, Takahiro Arima

Research output: Contribution to journalArticlepeer-review

163 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1582-1591
Number of pages10
JournalEuropean Journal of Human Genetics
Issue number12
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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