title: Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.
abstract: LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice.
  
  
  
  Lrp2+/-mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1-13C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS.
  
  
  
  The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment.
  
  
  
  Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta.
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Zwier
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Baardman
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.|Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: T H
authors.initials: TH
authors.lastname: van Dijk
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Jurdzinski
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Wisse
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: V W
authors.initials: VW
authors.lastname: Bloks
authors.affiliation: Center for Congenital Heart Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: R M F
authors.initials: RMF
authors.lastname: Berger
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: DeRuiter
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: A K
authors.initials: AK
authors.lastname: Groen
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Plösch
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D002784:Cholesterol
keywords: cholesterol; fetus; lipoprotein; placenta; transport