Nutrition and placental functions

The placenta has multiple functions that are very important for normal fetal growth. For example, the placenta consumes up to 50% of oxygen and glucose extracted from the uterine circulation. When substrate availability is reduced, the placenta reduces the consumption of oxygen and glucose and increases the consumption of amino acids (Owens et al, 1989), establishing a complex balance of nutrient utilization between itself and the fetus. This is achieved by the fetus becoming catabolic and providing the substrate needed for a placental oxidative metabolism.

Placental transport of nutrients to the fetus

All of the nutrients used by the fetus for energy production and growth are transported by the placenta (Battaglia and Meschia, 1986). Some (e.g. glucose and fatty acids) are transported by facilitative transport proteins according to maternal-to-fetal concentration gradient kinetics. Others, like amino acids, are transported by active energy-dependent transporter proteins. Gases are transported by passive diffusion. Many other nutrients (e.g. lactate and ammonia) are products of placental metabolism.

Glucose is the most important carbohydrate transported to the fetus by the placenta. Smith et al (1992) reported that this transport is accomplished by the GLUT 1, a facilitative transporter protein that shows specificity for glucose among hexoses. Simmons et al (1979) showed that the arterial plasma glucose concentration gradient from the mother to the fetus is the physiological driving force that determines placental glucose uptake and transfer to the fetus. The capacity for placental transfer increases with gestational age (Molina et al, 1991, Figure 1), as does the placental concentration of GLUT 1 transporter (Morris et al, 1985). If hypoxic stress (hypertension) or persistent placental hypoglycemia (maternal starvation) is present, fetal catecholamine secretion may promote glucogenolysis and decrease fetal insulin concentration as well as glucose utilization. In prolonged hypoglycemia even fetal glucogenolysis has been reported (Narkewicz et al, 1993). Hypoxic or hypoglycemic states could result in IUGR.

Nitrogen is supplied to the fetus by placental transport of amino acids. Amino acid transport occurs by energy-dependent processes via amino acid transport proteins (Yudilevich and Sweiry, 1985). The placenta does not just function as an amino acid pump; rather, it selectively takes up, metabolizes and transports each amino acid individually (Carter et al, 1991). This is one of the most important advances in our understanding of placental amino acid transport, providing evidence of the fundamental role of the placenta as a metabolic regulator of fetal nutrient supply. Such a regulatory role probably has important implications for growth and protection of the fetus during critical developmental periods. For most of the amino acids, concentrations in fetal plasma exceed those in maternal plasma. Based on this energy-dependent condition, it is not surprising that experimental maternal hypoxemia in animal models results in decreased transport of some amino acids to the fetus (Milley, 1988). Studies in pregnant sheep also indicate that amino acid transport to the fetus may be limited when uterine blood flow (UBF) is reduced chronically, as may be the case during hypertension that occurs during pregnancy (Lang et al, 1994), or when the mother is made chronically hypoglycemic (Carver et al, 1993).

The human placenta also appears to have a great capacity for lipid transfer, using transporters for specific fatty acids and more complex pathways. These pathways include lipoprotein dissociation with placental lipoprotein, lipase and triglyceride uptake and metabolism (Coleman, 1986). Lipids are released into the fetal plasma as free fatty acids, or lipoproteins. In humans, fetal patterns of essential fatty acids and structural lipids correlate directly with the fatty acid-lipid composition of the maternal plasma, and thus, with the maternal diet (Davis, 1923). However, the role of placental lipid metabolisms in fetal growth is unknown.

Figure 1. Graphic illustration of the interaction between development, and placental glucose transfer capacity, fetal glucose demand, and fetal glucose concentration from the second trimester to late third trimester in a sheep model.

The glucose transfer capacity increases with gestation (slope at 76.5 days, compared with slope at 131.5 days). Placental glucose transfer increases with gestation (points A and B). As fetal growth continues there are additional demands for glucose (point C). The actual glucose supply to the fetus is illustrated at point D. (From: Molina RA et al, Am J Physiol 261:R697-R704, 1991).