Figure 1. Some key placental signaling pathways and nutrient transporters.

The syncytiotrophoblast consists of two polarized plasma membranes, microvillous plasma membrane (MVM) and basal membrane (BM), that express an array of transport proteins that mediate maternal-to-fetal transfer of amino acids, glucose, and fatty acids. The uptake of nonessential and essential amino acids from maternal circulation across the MVM is mediated by System A (SNAT1, 2, 4) and System L (LAT1, 2) transport systems that are trafficked to the plasma membrane as a result of activation of insulin/IGF-1 and mTOR signaling. GLUT-1 is highly expressed in the MVM and BM of the syncytiotrophoblast and is considered the primary glucose transporter in the human placenta at term. Maternal triglycerides are hydrolyzed into FFA by membrane-bound lipases and transferred across the MVM by FAT/CD36 and FATPs. Internalized FFA are transferred to the BM by FABPs for export into fetal circulation. Akt, Protein Kinase B; Cdc/Rac1, cell division control protein/ras-related C3 botulinum toxin substrate 1; EAA, essential amino acids; FA, fatty acids; FABPs, fatty acid binding proteins; FAT/CD36, fatty acid translocase/cluster of differentiation 36; FATPs, fatty acid transport proteins; GLUT1, glucose transporter 1; IGF-1, insulin-like growth factor; IR, insulin receptor; IRS-1, insulin receptor substrate 1; LAT 1, L-amino acid transporter 1, 2; LPL, lipoprotein lipase, mTORC1, mechanistic target of rapamycin complex 1; mTORC2, mechanistic target of rapamycin complex 2; Nedd4–2, neuronal precursor cell-expressed, developmentally down-regulated gene 4 isoform 2; NEAA, non-essential amino acids; SNAT 1, Sodium-coupled neutral amino acid transporter 1, 2, 4; TG, triglycerides. Courtesy of KIMEN Design4Research, with permission.