Intergenerational and transgenerational epigenetic mechanisms shaping livestock production and reproduction.

Epigenetic reprogramming during gametogenesis and early embryogenesis involves genome-wide erasure and re-establishment of DNA methylation, ensuring developmental plasticity. However, specific genomic regions, such as imprinted loci and transposable elements, can escape this reprogramming, allowing environmentally induced epigenetic marks to persist and potentially transmit across generations. This review summarizes current advances in intergenerational and transgenerational epigenetic inheritance in mammals, with emphasis on nutritional influences. Seminal studies from the Dutch famine cohorts and the viable yellow agouti (Avy) mouse model established that maternal diet could remodel the epigenome and induce long-term phenotypic effects. Extending these findings to livestock, our recent studies demonstrate that both maternal and paternal methionine supplementation alter DNA methylation and influence growth and fertility traits in sheep. Notably, some epigenetic marks and phenotypic effects persist through the F4 generation, providing rare evidence of stable transgenerational epigenetic inheritance in a mammalian livestock model. These findings highlight nutrition as a powerful modulator of the germline and embryonic epigenome. Understanding how dietary factors shape heritable epigenetic variation offers new opportunities to improve animal health, fertility, and productivity, while providing fundamental insights into the mechanisms and evolutionary relevance of epigenetic inheritance in mammals.