Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome

Katie T. Jenkins, Louise S. Merkens, Matthew R. Tubb, Leslie Myatt, W. Sean Davidson, Robert D. Steiner, Laura A. Woollett

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts. It was unclear whether cholesterol could be effluxed to fetuses with SLOS since lipoprotein levels are often very low. To answer this question, cord blood was collected from the placentas of an SLOS fetus and unaffected fetuses just after delivery. Plasma cholesterol concentrations were very low in the affected fetus; cholesterol, 7-dehydrocholesterol, and 8-dehydocholesterol concentrations were 14.1, 4.5, and 5.2 mg/dl, respectively. The HDL from the fetal SLOS effluxed ≈50% more cholesterol from a trophoblast cell line, were smaller in size, and had a lower cholesterol to phospholipid ratio as compared to HDL from unaffected fetuses or adults. Plasma from the SLOS fetus effluxed cholesterol to a similar percentage as unaffected fetal plasma or adult plasma, possibly due to fewer HDL particles as demonstrated in previous SLOS patients. These novel data demonstrate that the cholesterol-deficient SLOS fetus is able to obtain cholesterol from trophoblasts at a time when cholesterol is playing a critical role in development, and has implications for design of treatments for cholesterol deficiency syndromes as well as understanding of prenatal cholesterol transport in humans.

Original languageEnglish (US)
Pages (from-to)240-247
Number of pages8
JournalMolecular Genetics and Metabolism
Volume94
Issue number2
DOIs
StatePublished - Jun 2008

Keywords

  • BeWo cells
  • Cholesterol transport
  • Fetus
  • Pregnancy
  • Trophoblast

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Fingerprint Dive into the research topics of 'Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome'. Together they form a unique fingerprint.

Cite this