The study investigates the conservation of methylation reprogramming in mammalian development and examines whether this process occurs aberrantly in cloned embryos. It is found that genome-wide methylation reprogramming, including active demethylation of the paternal genome and subsequent de novo methylation, is conserved across several mammalian species. However, in cloned embryos, the reprogramming process is often incomplete. In normal embryos, methylation levels decrease during cleavage and then increase de novo by the 16-cell stage. In contrast, cloned embryos show reduced methylation initially but fail to undergo further demethylation. Instead, they exhibit premature de novo methylation and nuclear reorganization, leading to hypermethylated nuclei resembling those of the somatic donor cells. This aberrant reprogramming may contribute to the low efficiency of cloning, as it can lead to altered gene expression and developmental abnormalities. The study highlights the importance of accurate epigenetic reprogramming for successful cloning.The study investigates the conservation of methylation reprogramming in mammalian development and examines whether this process occurs aberrantly in cloned embryos. It is found that genome-wide methylation reprogramming, including active demethylation of the paternal genome and subsequent de novo methylation, is conserved across several mammalian species. However, in cloned embryos, the reprogramming process is often incomplete. In normal embryos, methylation levels decrease during cleavage and then increase de novo by the 16-cell stage. In contrast, cloned embryos show reduced methylation initially but fail to undergo further demethylation. Instead, they exhibit premature de novo methylation and nuclear reorganization, leading to hypermethylated nuclei resembling those of the somatic donor cells. This aberrant reprogramming may contribute to the low efficiency of cloning, as it can lead to altered gene expression and developmental abnormalities. The study highlights the importance of accurate epigenetic reprogramming for successful cloning.