DISRUPTION OF PRIMARY IMPRINTING DURING OOCYTE GROWTH LEADS TO THE MODIFIED EXPRESSION OF IMPRINTED GENES DURING EMBRYOGENESIS

Parthenogenetic embryos, which contained one genome from a neonate-der ived non-growing oocyte and the other from a fully grown oocyte, devel oped to day 13.5 of gestation in mice, 3 days longer than previously r ecorded for parthenogenetic development, To investigate the hypothesis that disruption of primary imprinting during oocyte growth leads to t he modified expression of imprinted genes and this parthenogenetic phe notype, we have examined Peg1/Mest, Igf2, Peg3, Snrpn, H19, Igf2r and excess p57(KIP2). We show that paternally expressed genes, Peg1/Mest, Peg3 and Snrpn, are expressed in the parthenotes, presumably due to a lack of maternal epigenetic modifications during oocyte growth. In con trast, the expression of Igf2, which is repressed in a competitive man ner by transcription of the H19 gene, was very low Furthermore, we sho w that the maternally expressed Igf2r and p57(KIP2) genes were repress ed in the alleles of the nongrowing oocyte indicating maternal modific ations during oocyte growth are necessary for its expression. Thus, ou r results show that primary imprinting during oocyte growth exhibits a crucial effect on both the expression and repression of maternal alle les during embryogenesis.