Abstract
Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both genes were expressed in placenta and microsomal extracts from human placenta contained triglyceride transfer activity, indicating expression of bioactive MTP. To detect lipoprotein secretion, biopsies from term placentas were placed in medium with [(35)S]methionine and [(35)S]cysteine for 3-24 h. Upon sucrose gradient ultracentrifugation of the labeled medium, fractions were analyzed by apoB-immunoprecipitation. (35)S-labeled apoB-100 was recovered in d approximately 1.02-1.04 g/ml particles (i.e. similar to the density of plasma low density lipoproteins). Electron microscopy of negatively stained lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway of lipid transfer from the mother to the developing fetus.
Highlights
The most efficient system for delivery of lipids from a tissue to the blood is the formation and secretion of apolipoprotein B1-containing lipoproteins
The importance of apolipoprotein B (apoB)-containing lipoprotein secretion is evident in the liver and intestine, where both apoB and microsomal triglyceride transfer protein (MTP) are needed to export large amounts of lipids for usage in peripheral tissues [2, 5, 6]
The importance of lipoprotein secretion from the yolk sac in mice is emphasized by the observation that both apoB and MTP knockout mice die in utero [11, 12]
Summary
To the blood is the formation and secretion of apolipoprotein B (apoB)1-containing lipoproteins. The importance of apoB-containing lipoprotein secretion is evident in the liver and intestine, where both apoB and microsomal triglyceride transfer protein (MTP) are needed to export large amounts of lipids for usage in peripheral tissues [2, 5, 6]. We speculated that even though rodent placentas express only very low levels of apoB and MTP [7, 8], the transfer of lipids from mother to fetus in humans could be mediated, at least in part, by apoB-containing lipoprotein secretion from the placenta. This hypothesis was addressed by characterizing human term placental biopsies with respect to mRNA and protein expression of MTP and apoB and secretion of newly formed apoB-containing lipoproteins
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