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Journal of Lipid Research, Vol. 50, 1146-1155, June 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

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^**, Friedhelm Schroeder and Laura A. Woollett^1,*

^* Department of Pathology and Laboratory Medicine, University of Cincinnati Medical School, Cincinnati, OH 45237
Department of Obstetrics/Gynecology, University of Cincinnati Medical School, Cincinnati, OH 45237
Department of Internal Medicine and Division of Gerontology, University of Maryland School of Medicine and the Baltimore Veterans Affairs Medical Center, Geriatrics Research, Education, and Clinical Center, Baltimore, MD 21201
^** Department of Pharmaceutical Sciences and Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536
Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843

These studies were supported by grants HD34089 (LAW) and GM31651 (FS) from the NIH and 053025N from the AHA (GAG).

Published, JLR Papers in Press, January 3, 2009.

¹ To whom correspondence should be addressed. e-mail: laura.woollett{at}uc.edu

The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study 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. 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 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 liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, 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 placental NPC1L1 expression.

Supplementary key words placenta • yolk sac • Smith-Lemli-Opitz Syndrome • low density lipoprotein • high density lipoprotein • liver X receptor • NPC1 Like 1

Abbreviations: dpc, days postconception; FCR, fractional catabolic rate; LDLR, LDL receptor; NPC1, Niemann-Pick C1; NPC1L1, NPC1 Like Protein; SCP, sterol carrier protein; Shh, sonic hedgehog; SLOS, Smith-Lemli-Opitz Syndrome; SREBP-2, sterol regulatory element binding protein-2

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