Maternal nutrition’s impact on liver transcriptome in beef cattle offspring is still underexplored. We investigated the long-term effects of maternal nutrition strategies on the liver transcriptome of pre-slaughter Nelore bulls. Pregnant cows were divided into three groups, each receiving different nutritional regimens: NP (control, only mineral supplementation), PP (late gestation protein–energy supplementation), and FP (protein–energy supplementation throughout pregnancy). Liver samples were collected from male offspring aged 22.5 ± 1 months and analyzed using RNA-Seq (n = 5 per treatment). Principal component analysis (PCA) and differential gene expression analysis were carried out in an R statistical environment. Genes were considered significant when FDR < 0.05. The over-representation analysis (ORA) was performed using the clusterProfiler package from R. Metabolic pathways were considered significant when the Q-value < 0.1. The PCA showed overlapping clusters among the groups. We identified 16 differentially expressed genes (DEGs) associated with PP × NP contrast, four with FP × NP, and two with FP × PP. The ORA revealed two significant pathways (thiamine and butanoate metabolism). The identified genes and pathways were associated with vitamins, energy, oxidative metabolism, and immune function. This study emphasizes the more significant long-term effects of the PP treatment on the offspring’s liver transcriptome compared to the FP treatment.

Fetal programming suggests that maternal nutrition during gestation influences offspring growth, development, and productivity. This study evaluated the effects of prenatal protein-energy supplementation on the lifetime performance of Nellore cattle. Twenty-eight nulliparous heifers were inseminated and assigned to one of two groups: Non-Programmed; receiving only mineral supplementation; or Fetal Programmed (FP); receiving additional protein-energy supplementation throughout gestation. Cows in the FP group maintained significantly better body condition score during gestation (p < 0.01), and their calves exhibited greater body weight (BW) during the first 56 days (p < 0.05) and a tendency to grow to a greater BW up to 250 days (p < 0.10) in addition to improved morphological traits, such as increased rump width and length at 45 days of age (p ≤ 0.02). However, these advantages were not sustained in later growth stages, as no significant differences were observed in final body weight, ultrasound carcass traits, or overall feedlot performance. These findings suggest that while prenatal nutrition can influence early developmental traits, its long-term impact on offspring performance may be limited under consistent postnatal management. Nonetheless, the limited sample size, combined with the absence of molecular data and individual feed intake and efficiency measurements, constrains a more comprehensive interpretation of the programming effects on offspring performance. Further research is needed to explore the molecular mechanisms of fetal programming, particularly its epigenetic effects and interactions with postnatal nutrition, to optimize strategies for improving the efficiency and sustainability of beef cattle.