Epigenetically immature oocytes lead to loss of imprinting during embryogenesis

Yayoi Obata, Hitoshi Hiura, Atsushi Fukuda, Junichi Komiyama, Izuho Hatada, Tomohiro Kono

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Loss of imprinting (LOI) is occasionally observed in human imprinting disorders. However, the process behind the LOI is not fully understood. To gain a better understanding, we produced embryos and pups from mouse oocytes that lacked a complete methylation imprint using a method that involved transferring the nuclei of growing oocytes into the cytoplasm of enucleated fully grown oocytes following in vitro fertilization (IVF). We then analyzed the imprinting statuses. Our findings show that the incomplete methylation imprint derived from growing oocytes results in epigenetic mosaicism or a loss of methylation imprint (LOM) at maternal alleles in embryos. In some embryos, both hypo- and hypermethylated maternal Kcnq1ot1 alleles were detected, whereas either hypo- or hypermethylated maternal Kcnq1ot1 alleles were detected in others. Such tendencies were also observed at the Igf2r and Mest loci. Gene expression levels of imprinted genes were linked with their methylation statuses in some but not all embryos. Possible explanations of the inconsistency between the data from DNA methylation and gene expression include epigenetic mosaicism in embryos. Pups were successfully produced from growing oocytes at a quite low frequency. They exhibited an obese phenotype and LOI with respect to Igf2r, Snrpn and Mest. Our finding suggests the possibility that LOI/LOM at maternal alleles in human concepti could be derived from epigenetically immature/mutated oocytes.

Original languageEnglish
Pages (from-to)327-334
Number of pages8
JournalJournal of Reproduction and Development
Volume57
Issue number3
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • DNA methylation
  • Gene expression
  • Genomic imprinting
  • Growing oocyte
  • Loss of imprinting (LOI)

ASJC Scopus subject areas

  • Animal Science and Zoology

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