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, Laura A. Woollett

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1146-1155
Number of pages10
JournalJournal of lipid research
Volume50
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • High density lipoprotein
  • Liver X receptor
  • Low density lipoprotein
  • NPC1 Like 1
  • Placenta
  • Smith-Lemli-Opitz Syndrome
  • Yolk sac

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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