Gestational stage alters insulin and mTOR signaling in bovine maternal placentome and fetal liver

Understanding stage-specific regulation of placental and fetal metabolic signaling pathways is essential to elucidate mechanisms supporting fetal growth and developmental programming in dairy cattle. This study evaluated differences in protein abundance between mid-gestation and late-gestation in placentome and fetal liver in lactating Holstein cows. In placentome tissue, late-gestation was characterized by a marked decrease in phosphorylated ribosomal protein S6 (p-RPS6; P = 0.01), suggesting reduced signaling through the mTOR-RPS6 axis, which is involved in the regulation of protein synthesis. In contrast, proteins associated with cellular stress response and detoxification were significantly elevated, including heat shock protein 70 (HSP70; P = 0.01) and glutathione S-transferase Mu 1 (GSTM1; P = 0.03), suggesting enhanced oxidative stress defense and protein-folding capacity as gestation advances. In fetal liver, late-gestation exhibited a pronounced reduction in insulin signaling, evidenced by lower AKT abundance (P = 0.01). Additionally, the ratio of phosphorylated to total mTOR (P = 0.03) and p-RPS6 abundance (P = 0.01) were decreased, further supporting attenuation of anabolic signaling pathways. Conversely, total eukaryotic elongation factor 2 (eEF2) abundance increased (P = 0.01), potentially reflecting a compensatory mechanism to sustain translational capacity despite reduced upstream signaling. Collectively, these data indicate a shift from anabolic growth signaling toward enhanced stress adaptation and selective translational control in late-gestation. The coordinated downregulation of insulin/mTOR signaling alongside increased stress-response proteins highlights tissue-specific adaptations that may optimize fetal development under changing metabolic demands.