Developmental potential of mouse primordial germ cells

There are distinctive and characteristic genomic modifications in primordia l germ cells that distinguish the germ cell lineage from somatic cells. The se modifications include, genome-wide demethylation, erasure of allele-spec ific methylation associated with imprinted genes, and the re-activation of the X chromosome. The allele-specific differential methylation is involved in regulating the monoallelic expression, and thus the gene dosage, of impr inted genes, which underlies functional differences between parental genome s, However, when the imprints are erased in the germ line, the parental gen omes acquire an equivalent epigenetic and functional state. Therefore, one of the reasons why primordial germ cells are unique is because this is the only time in mammals when the distinction between parental genomes ceases t o exist. To test how the potentially imprint-free primordial germ cell nuclei affect embryonic development, we transplanted them into enucleated oocytes, Here we show that the reconstituted oocyte developed to day 9.5 of gestation, co nsistently as a small embryo and a characteristic abnormal placenta. The em bryo proper also did not progress much further even when the inner cell mas s was 'rescued' from the abnormal placenta by transfer into a tetraploid ho st blastocyst. We found that development of the experimental conceptus was affected, at least in part, by a lack of gametic imprints, as judged by DNA methylation and expression analysis of several imprinted genes. The eviden ce suggests that gametic imprints are essential for normal development, and that they can neither be initiated nor erased in mature oocytes; these pro perties are unique to the developing germ line.