Differential Demethylation of Paternal and Maternal Genomes in the Preimplantation Mouse Embryo: Implications for Mammalian Development

Higher eukaryotes are endowed with a diploid somatic genome. At fertilization the paternal and maternal genomes are combined, forming the new diploid organism. Nuclear transfer experiments in the 1980s (McGrath and Solter, 1984; Surani et al., 1986) demonstrated for the first time the functional non-equivalence of the two parental genomes in mammals. In contrast to many lower vertebrates, mammalian uniparental embryos cannot develop beyond mid-gestation. Androgenetic embryos, with two paternal genomes, are usually very stage-retarded but often have well developed mural trophoblast and yolk sac. Gynogenetic embryos, with two maternal genomes, can develop relatively normally to mid-term but are small and have very restricted trophoblast and yolk sac. In both cases there is no normal placental development. Because of opposing patterns of gene expression from maternal and paternal alleles of imprinted genes (Fundele and Surani, 1994; Tilghman, 1999), normal mammalian development requires the participation of both a maternal and a paternal genome. Genomic imprinting is thought to be a by-product of the unique fetal-maternal relationship in mammals to control the different parental interests on embryo development. Consistent with the parental conflict hypothesis (Moore and Haig, 1991), many paternally expressed genes enhance fetal growth, whereas maternally expressed genes inhibit growth.