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The DNA sequence can pass inheritable information to offspring by its precise replication during cell division. In mammals, DNA methylation mainly occurs in 5′-Cytosine-phosphate-Guanine-3′ (CpG) by adding a methyl group to the fifth carbon of the Cytosine (5mC). This mark is replicated at each cell division by the action of the catalytic enzyme named DNA methyltransferase 1 (DNMT1).

The earliest research regarding DNA methylation inheritance was documented in plants where DNA methylation was correlated to floral symmetry in Linaria vulgaris, proving that the Linaria Cycloidea (Lcyc) gene methylation mutation could be inherited for several generations (Cubas et al., 1999). When talking about DNA methylation inheritance, it is pivotal to distinguish between intergenerational and transgenerational inheritance. The former mainly indicates F0 to F1 transmission but with one exception: the germline (F2) of a fetus (F1) can respond to environmental factors while in utero. Under this condition, the F0, F1, and the future F2 (germline of the fetus) are all exposed to the altered environment, thereby constituting intergenerational inheritance. Transgenerational inheritance means that the altered epigenetic modification can be inherited even if the successive offspring are not directly exposed to the same environment.

This paper summarizes the recent progress of 5mC inheritance research in humans and animals, emphasizing dairy cows. The first section of this review summarizes the potential mechanisms involved in DNA methylation inheritance, while sections two and three discuss paternal and maternal 5mC inheritance. The remaining sections include a description of possible mechanisms of mitochondrial DNA methylation inheritance, and 5mC inheritance in different species. Finally, the challenges and limitations of research in DNA methylation inheritance are presented.