title: Epigenetically immature oocytes lead to loss of imprinting during embryogenesis.
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.
authors.affiliation: Department of BioScience, Tokyo University of Agriculture, Tokyo, Japan. ylobata@nodai.ac.jp
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Obata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hiura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukuda
authors.forename: Junichi
authors.initials: J
authors.lastname: Komiyama
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kono
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D020869:Gene Expression Profiling; D056426:Genetic Loci; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D051379:Mice; D009030:Mosaicism; D009765:Obesity / Q000235:genetics; D009865:Oocytes / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: C513121:IGF2 protein, mouse; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D011506:Proteins; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins; D007335:Insulin-Like Growth Factor II