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

Scientific Reports 2017 July 13
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 < 0.001) in SR-BI(-/-) embryos and normalized ROS and gene expression levels. In sum, our results suggest the involvement of SR-BI in the maternal provision of embryonic vitamin E to the mouse embryo during neural tube closure.

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