Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the golden syrian hamster

Katie T. Burke, Perry L. Colvin, Leslie Myatt, Gregory A. Graf, Friedholm Schroeder, and Laura A. Woollett

Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507

Corresponding Author: laura.woollett{at}uc.edu

The fetus has a high requirement for cholesterol and, as such, synthesizes cholesterol at elevated rates during this rapid growth phase. Recent studies suggest that fetal cholesterol can be obtained from exogenous sources as well. The purpose of the studies presented here was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. LDL- and HDL-cholesterol uptake (µg/h) was ~3-fold greater in the placentas and yolk sacs of dams fed 2% added cholesterol compared to those fed no added cholesterol. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by way of the placenta and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated LXR, were found to be expressed in both the hamster and human placenta: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas, however. Thus, transport of maternal cholesterol to the fetus can be enhanced by increasing maternal lipoprotein-cholesterol concentrations, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possibly 3) increased NPC1L1 expression in the placenta.

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