Mechanism for Developmental Regulation by Genomic Imprinting in the Female Germ Line.

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In mammals, epigenetic modification of genomes during gametogenesis leads to an unequivalent expression of imprinted genes between parental alleles and necessary for term development. To understand the further insight into genomic imprinting we have done several lines of experiment. Firstly, to investigate when and how, precisely, maternal primary imprinting is established, we produced parthenogenetic embryos containing one genome from a non-growing or growth stage oocyte from 1- to 20-day old mice, and one from a fully-grown oocyte from adult mice. Using these embryos, expression analysis of eight imprinted genes, Snrpn, Znfl27, Ndn, Peg3, Igf2r, p57^<KIP2>, Peg1 and Impact, was conducted. The results show that the epigenetic markers for each imprinted gene are not imposed all together at a specific time during oocyte growth, but rather occurs within a wide range during the period from primary to antral follicle stage oocytes. The developmental ability of the constructed parthenogenet … More ic embryos is gradually reduced with the growth of nuclear donor oocytes. Thus, the present study clearly demonstrate that maternal primary imprinting occurs in a stepwise fashion for groups of imprinted genes during the oocyte growth stages. Secondly, we examined whether the regulation of H19 monoallelic expression enhances the survival of parthenogenetic embryos. The results clearly show that the ng/fg parthenogenetic embryos carrying the ng-oocyte genome that had been deleted by the H19 transcription unit successfully developed as live fetuses for 17.5 gestation days. Control experiments revealed that this unique phenomenon occurs irrespective of the genetic background effect. Histological analysis showed that the placenta of ng^<H19-KO>/fg^<WT> parthenotes was resulted in atrophia with sever negro-cytosis and other anomalies. The present results suggest that the cessation of H19 gene expression from the ng-allele causes the extended development and that functional defection of the placenta could be fatal for the ontogeny. Less