Deficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice Lacking Lipoprotein Receptor SR-BI

Abstract SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissue, specifically in trophoblast giant cells in the parietal yolk sac. We previously showed that approximately 50% of SR-BI−/− embryos fail to close the anterior neural tube and develop exencephaly, a perinatal lethal condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake during murine neural tube closure. Our results showed that SR-BI−/− embryos had a very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI−/− embryos with closed neural tubes (nSR-BI−/−) had high levels of reactive oxygen species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI−/− embryos were detected in SR-BI−/− with NTD (NTD SR-BI−/−). Reduced expression of Pax3, Alx1 and Alx3 genes was found in NTD SR-BI−/− embryos. Maternal α-tocopherol dietary supplementation prevented NTD almost completely (from 54% to 2%, p