Mvm Bm

Figure 3 Factors affecting nutrient transfer across the syncytiotrophoblast. These include: (1) maternal and fetal blood flow; (2) the nutrient concentration gradient across the syncytiotrophoblast; (3) the concentration of transport proteins to facilitate or actively transport nutrients; (4) the exchangeable surface area; (5) the rate of diffusion of some nutrients across membranes without the intervention of transport proteins; (6) metabolism (utilization and de novo synthesis) within the placenta; and (7) the rate of nutrient utilization by the fetal tissues.

and the presence of the same or similar transport systems to those in the tissues and organs of the adult, although there are some additional factors specific to the placenta (Figure 3). In particular, unlike most tissues in the adult where either uptake or export dominate at any given time, the syncytiotrophoblast whose primary function is transport has to do both simultaneously.

The placental transport systems for the macro-nutrients (carbohydrate, fat, and protein) have been extensively studied. Glucose transport within the placenta appears to be mediated exclusively by the GLUT1 transporter, which has been located on both the MVM and BM. GLUT3 and GLUT4 are also present in the placenta but not in the syncytiotro-phoblast itself. They are located on the vascular endothelium and the intravillous stromal cells, respectively. The syncytiotrophoblast also contains a wide range of amino acid transporters: system A, ASC, Asc, B0, b°,+, L, N, Gly, y+, y+L and Xag and fi. A number of fatty acid-binding proteins are also found in the placenta. Of these proteins FAT/ CD36 and FATP have been located to both the MVM and BM but there is also a placenta-specific protein (p-FABPpm), which has been located exclusively on the MVM. This p-FABPpm is similar in size (—40kDa) to the ubiquitous FABPpm found in most mammalian cells but it has a different amino acid composition.

The driving force that results in the net transfer of nutrients to the fetus is different for different nutrients and this is reflected in their transplacental gradients (Figure 4). Where the nutrient concentrations are lower in the cord than maternal blood this has been cited as a reason to supplement the mother but in many cases it is precisely this gradient that drives placental nutrient transfer. Glucose is thought to flow down a concentration gradient from the mother to the fetus and this process of 'facilitated diffusion' is mediated by GLUT1. Unlike glucose the concentration of most amino acids in the fetal circulation is greater than that in the maternal circulation suggesting some form of active transport. For many amino acids the concentration is even higher within the placenta than the fetal circulation and the key gradient generating step for amino acids is the active transport across the MVM. The amino acids can then diffuse down a concentration gradient into the fetal circulation, and to some extent back to the mother. The concentration of water-soluble vitamins and lactate in the fetal circulation also exceeds that in the maternal circulation.

Like glucose, the fats and fat-soluble vitamins also flow down a concentration gradient from the mother to the fetus mediated by the various fatty acid transport proteins. However, unlike glucose or the amino acids, fat-soluble compounds can also cross the syncytiotrophoblast, and all other membranes for that matter, by simple diffusion and partition without the intervention of a carrier protein. The role of the fatty acid-binding proteins appears to be to improve the efficiency of this process. The key factor in understanding the driving force for the placental transfer of fat-soluble nutrients is that these compounds are only sparingly soluble in water (13 |mM for C18:0 at 37 °C) and have to be transported in the plasma in hydrophobic binding sites on carrier proteins. The partition of fats between the maternal and fetal circulations is largely determined by the relative abundance of available hydrophobic binding sites within those compartments. Since only NEFA are thought to cross membranes it is the NEFA concentration gradient that is most relevant to the transplacental flow of fatty acids. The concentration of NEFA in the maternal plasma at term is around 3 times that in the fetal circulation but the concentration of its primary carrier protein, albumin, is actually 10-20% higher in the fetal circulation. This results in a ratio of NEFA to albumin on the fetal side of the placenta of around a quarter of that on the

Maternal circulation



Fetal circulation

Amino acids nonessential (64%)


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