The role of feed restriction on DNA methylation, feed efficiency, metabolome, biochemical profile and progesterone patterns in the female filial generation (F1) obtained from early feed restricted ewes (F0)

Farm animals dedicated to replacement purposes must be carefully managed and selected to ensure the best reproductive traits,thus avoiding potentially adverse effects due to developmental programming issues. DNA methylation profiles transmitted acrossgenerations allow researchers to decode epigenetic regulation mechanisms in mammals and identify novel candidate genescorrelated with phenotype differences in both, dams and offspring. Therefore, improving knowledge in the field of epigenetics andtransgenerational effects caused by pre- and postnatal early nutritional events (e.g., feed restriction) is crucial for refiningstrategies dedicated to animal breeding. In the present study we determined differences in the biochemical profile, metabolomeand global blood methylation patterns of F0 (between ewe lambs with or without early feed restricted) and F1 (female lambs bornfrom F0) by reduced representation bisulfite sequencing (RRBS) technology. Our data show that functional categories such as thoserelated to cellular processes, phosphorylation, nervous system, immunity response or reproductive function were significantlyenriched in the F1-feed restricted (F1-RES) lambs due to differences in the methylation of genes in these categories. These F1-RESlambs did not show differences in feed efficiency during the replacement period but presented higher levels of insulin andtriglycerides and reduced concentration of progesterone, whereas the metabolome profile demonstrated variations in the bileacid composition of both F1 groups. Taken together all these results suggest that transgenerational effects caused by early feedrestriction of dams (F0) may persist in the F1 female lambs with negative consequences on genes involved in several (cellular)processes including reproductive traits.