Linoleic Acid Transport by Human Placental Syncytiotrophoblast Membranes

Abstract

The placenta syncytiotrophoblast is the site of exchange of nutrients, lipids and minerals between the mother and the fetus. In order to characterize the transport of fatty acids by the placenta, we purified bipolar syncytiotrophoblast brush border and basal plasma membranes from human placenta. These purified brush border and basal plasma membranes enriched 3-fold and 22-fold, respectively, in sodiudpotassium-ATPase and 27-fold and 6-fold in alkaline phosphatase activity, compared with the placental homogenates. Fatty acid transport was performed at different fatty acid albumin ratios to evaluate the optimal uptake conditions. The maximal transport efficiency, for linoleic acid bound to albumin by sonication, was obtained with a 6 : 1 fatty acidalbumin ratio in brush border and basal plasma membranes. The linoleic acid transport observed with brush border membranes followed Michaelis-Menten kinetics, with a Michaelis constant of 7.89 ? 0.01 pM and a maximal incorporation rate of 30.80 ? 6.39 pmol . mg-' . min-I. Linoleic acid transport was very low in basal plasma membranes and we obtained a Michaelis constant of 0.95 2 0.01 yM and a maximal incorporation rate of 1.62 +-5.06 pmol . mg-' . mine '. In order to show that linoleic acid accumulated within brush border and plasma membrane vesicles, and to eliminate the possibility of a non-specific binding of fatty acid to these membranes, we demonstrated by an osmolarity experiment, the decrease of the linoleic acid transport in brush border and basal plasma membranes obtained in the presence of 455 pM essential fatty acid at 23°C for 180 min. The results presented in this study suggest that linoleic acid is transported significantly by syncytiotrophoblast brush border membranes and basal plasma membranes. Thus, it may represent a unidirectional transport from mother to fetus through the brush border membranes facing the mother, followed by transport at a slower rate through basal plasma membranes facing the fetus.Fatty acids are required for adequate fetal development and growth. These fatty acids can be synthesized by the placenta [I, 21 or can be provided by external sources including the maternal circulation. The amount of fatty acids transported by the placenta to the fetus varies between species [3]. In the ruminant and feline fetus, with epitheliochorial and hemoendothelial placentation, respectively, the amount of fatty acids transported by the placenta is less important than in species with hemochorial placentation (e.g. humans) [4-61. In a review article, Coleman has reported that fatty acid transport seems to be affected by maternal nutrition and stages of gestation [7]. Essential fatty acids are provided only by the maternal diet because the metabolic enzymes required for their synthesis are not present in fetuses of mammals [7, 81. In the last trimester of pregnancy, these essential fatty acids are very important for the growth and the development of the nervous system [9, lo], for the elaboration of cellular Correspondence to J. Lafond, Universite du...

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“…Since P, O and L have been shown to associate directly with albumin [19,23,24], we assayed the POL cocktail to see if it merges with human recombinant albumin to induce LDs. MALME-3M cells were incubated in the presence of POL, recombinant albumin only, or in combination with both POL and albumin.…”

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“…They also observed the presence within the syncytiotrophoblast of cytoplasmic binding proteins first identified in the heart (H-FABP) and liver (L-FABP) (Campbell & Dutta-Roy, 1995;Campbell et al, 1998a;Dutta-Roy, 2000). The largely symmetric arrangement of fatty acid transfer proteins on microvillous and basal membranes and NEFA-binding sites in both circulations suggests the possibility of bidirectional transfer of fatty acids across the syncytiotrophoblast and this is borne out by in vitro (Lafond et al, 1994(Lafond et al, , 2000 and in vivo studies (Hendrickse et al, 1985) of AA transport.…”

“…The placenta has the capacity to transfer fatty acids in either direction (Hendrickse et al, 1985;Lafond et al, 1994), but net transfer is normally from the mother to the fetus and this is driven by the relative concentrations of NEFA and its binding sites at the microvillous and basal membranes (Patel et al, 1997;Haggarty, 2002). The NEFA concentration difference between the maternal and fetal circulation increases throughout gestation until term when the concentration of NEFA in the maternal plasma at term is approximately three times that in the fetal circulation.…”

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“…Placental transfer of fatty acids has been studied in humans using vesicles prepared from syncytiotrophoblast of term placentas (26,27), by perfusion of term placentas in vitro (19,20), by determining the expression and specific fatty acid affinity of fatty acid binding proteins (5,10,29,36), or by comparing paired maternal and umbilical cord plasma fatty acid profiles either under basal conditions or after fatty acid supplementation (38). In rats, transplacental fatty acid transport has been studied by examining the effects of changes in maternal dietary fatty acids on the fatty acid profiles of fetal tissue (16,31), the expression of fatty acid regulatory proteins in placenta and trophoblast cell culture models (24), and transfer of fatty acids from palmitic acid (PA) or triacylglycerol in a short-term perfusion system in situ (21).…”