Journal
JOURNAL OF REPRODUCTION AND DEVELOPMENT
Volume 57, Issue 3, Pages 327-334Publisher
SOCIETY REPRODUCTION & DEVELOPMENT-SRD
DOI: 10.1262/jrd.10-145A
Keywords
DNA methylation; Gene expression; Genomic imprinting; Growing oocyte; Loss of imprinting (LOI)
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21780252]
- Grants-in-Aid for Scientific Research [21780252] Funding Source: KAKEN
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Loss of imprinting (LOT) is occasionally observed in human imprinting disorders. However, the process behind the LOT 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 Kcnqlot1 alleles were detected, whereas either hypo- or hypermethylated maternal Kcnqlot1 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 Most. Our finding suggests the possibility that LOI/LOM at maternal alleles in human concepti could be derived from epigenetically immature/mutated oocytes.
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