Regulation of nutrient transport across the placenta

Abstract

Abnormal fetal growth, both growth restriction and overgrowth, is associated with perinatal complications and an increased risk of metabolic and cardiovascular disease later in life. Fetal growth is dependent on nutrient availability, which in turn is related to the capacity of the placenta to transport these nutrients. The activity of a range of nutrient transporters has been reported to be decreased in placentas of growth restricted fetuses, whereas at least some studies indicate that placental nutrient transport is upregulated in fetal overgrowth. These findings suggest that changes in placental nutrient transport may directly contribute to the development of abnormal fetal growth. Detailed information on the mechanisms by which placental nutrient transporters are regulated will therefore help us to better understand how important pregnancy complications develop and may provide a foundation for designing novel intervention strategies. In this paper we will focus on recent studies of regulatory mechanisms that modulate placental transport of amino acids, fatty acids, and glucose.

Figure 1

The syncytiotrophoblast represents the primary barrier for transfer of nutrients from mother to fetus. Maternal blood pools in the intervillous space and bathes the microvillous membrane (MVM). The basal plasma membrane (BM) of the syncytiotrophoblast is oriented toward the fetal circulation. Transporters mediating the transfer of amino acids, glucose (GLUTs), and fatty acids (FATPs) are expressed in both plasma membranes of the syncytiotrophoblast. For transfer of lipids, extracellular lipases release fatty acids from maternal lipoproteins and intracellular binding proteins (FABPs) guide the fatty acids within the cytosol of the syncytiotrophoblast.

Figure 2

Placental function is likely regulated by numerous factors of fetal, maternal, and placental origin. Fetal signals affecting placental function include IGF-II and PTHrp. The effects of maternal factors, including adipokines, hormones, and nutrient levels, on placental function have been investigated in various models such as cultured trophoblast cells, placental explants, and perfused placenta. The placenta also expresses a wide array of molecules which are released into both fetal and maternal circulations. These substances may impact on the placenta itself in an autocrine/paracrine fashion. Integration of numerous, and sometimes divergent, signaling by intracellular regulatory pathways such as mTOR, PPAR, and STAT has been demonstrated to affect placental nutrient transport.