Maternal–Fetal Cholesterol Transport in the Placenta

Abstract

See related articles, pages 600–608 The transport of cholesterol from mother to fetus across the placental barrier has long been neglected. Although cholesterol is of vital importance for fetal development as a key constituent of cell membranes, precursor of steroid hormones and metabolic regulators (oxysterols), and a modulator of hedgehog signaling, it was generally assumed that most of it is synthesized de novo by the fetus and, to a lesser extent, by cells on the fetal side of the placenta. A contribution of placental cholesterol to fetal growth was supported by the fact that LDL-cholesterol concentrations in the umbilical cord vein (which delivers placental blood to the fetus) are greater than those in umbilical arteries,1 and by the ability of placental cells to secrete apolipoprotein (apo)B-containing particles.2 On the other hand, the case against maternal cholesterol transfer was based on the observation that the placental barrier is impermeable to labeled LDL and other lipoprotein particles and that genetically normal offspring of hypercholesterolemic mothers generally have very low cholesterol levels at term birth, whereas maternal cholesterol tends to be highest in the third trimester. Given the essential role of independent cholesterol synthesis, it is not surprising that most of the known genetic defects of cholesterol biosynthesis in fetuses severely impact their development and survival. The one exception is the Smith–Lemli–Opitz syndrome (SLO), a defect in the conversion of 7-dihydrocholesterol to cholesterol.3 Children with SLO are born relatively healthy and must therefore have obtained a minimum of cholesterol from the mother. Interest in potential mechanisms transporting cholesterol from mother to fetus was further stimulated by the recognition that maternal hypercholesterolemia, even if limited to …