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 approximately 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.