Genome-wide methylation patterns in normal and uniparental early mouse embryos.

In the normal diploid mouse embryo, active demethylation of the paternal genome but not of the maternal genome occurs within only a few hours and in a highly coordinated fashion as the zygote proceeds through the first G1 phase. This zygotic demethylation may be necessary to reprogram the sperm genome for somatic development. Immunofluorescence staining with an antibody against 5-methylcytosine shows that the cellular machinery of the fertilized egg cannot demethylate the second maternal genome in parthenogenetic, gynogenetic and triploid digynic embryos or remethylate the additional (already demethylated) paternal genome in androgenetic and triploid diandric embryos. This suggests that differential zygotic demethylation results from differences in the remodeling of paternal and maternal chromatin structures after fertilization, i.e. sperm nuclear decondensation and protamine-histone exchange. A proportion of embryos derived from normal matings display abnormal methylation patterns some of which are indistinguishable from those in androgenetic or gynogenetic embryos. We conclude that methylation reprogramming defects in mammalian zygotes contribute to the high incidence of early pregnancy failure.