Interactions between milk and trophoblast mTORC1 signaling. Leucine (Leu) and glutamine (Gln) derived from whey protein hydrolysis increase serum insulin. Milk casein increases serum IGF-1. Leucine, insulin and IGF-1 stimulate trophoblast mTORC1. Milk consumption is associated with placental weight gain, which is related to increased serum levels of human placental lactogen (HPL). HPL via STAT5/SOCS signaling as well as increased milk-mediated mTORC1/S6K1 signaling induce insulin resistance enhancing the glucose gradient to the fetus. Increased trophoblast mTORC1 and HPL stimulate placental expression of FGF21 upregulating GLUT1. Milk consumption during pregnancy exaggerates glucose transfer to the fetus. Trophoblast mTORC1 stimulates the expression of L-type amino acid transporters (LAT) (dotted line). Thus, milk intake during pregnancy overstimulates diaplacental flux of glucose and BCAAs promoting mTORC1-driven fetal overgrowth. Bovine exosomal microRNA-21 (miR-21) reaches maternal circulation and may thus decrease trophobast PTEN expression thereby enhancing trophoblast mTORC1 signaling.