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 tissueScavenger Receptor Class B type I (SR-BI) is the main receptor for high density lipoproteins (HDL), and numerous studies have described its role in mediating the bidirectional transport of lipids between these lipoproteins and cells 1 . In the liver, SR-BI is involved in the uptake of cholesterol from HDL and its excretion in bile, the final step in reverse cholesterol transport. SR-BI also participates in the uptake of cholesterol in steroidogenic tissues, such as the adrenal glands and ovaries, to be used as a substrate for steroid hormone synthesis 2 . Important information on the roles of SR-BI other than in cholesterol homeostasis and cholesterol provision for steroidogenesis, such as platelet aggregation, erythrocyte maturation and oocyte meiosis, has been generated from the SR-BI knock out (SR-BI −/− ) mouse since it was generated almost two decades ago 3 .In generating SR-BI −/− mice via heterozygous intercrosses, researchers noted that the proportion of weaned homozygous null mice was half that expected by the Mendelian ratio 3 . This evidence, together with the fact that SR-BI is present in murine trophoblasts involved in maternal-foetal nutrient exchange at different stages of gestation 4 , led researchers to postulate that this HDL receptor might be involved in embryonic development. We recently showed that nearly 50% of SR-BI −/− embryos fail to close the anterior neural tube and develop cranial NTD and exencephaly 5 , leading to perinatal death, which explains the deviation from the Mendelian ratio previously reported in weaned SR-BI null mice 3 . Among the spectrum of defective neurulation conditions conferred by abnormal closure at different portions of the neural tube, only cranial NTD is observed in SR-BI −/− embryos.During murine early development, SR-BI is not detected in the embryo itself but rather in trophoblast giant cells (TGC) from the parietal yolk sac 4,5 . TGC play a critical role in embryonic uptake of various nutrients from the maternal blood supply before the establishment of a mature placenta 6 . Despite the prominent role of SR-BI

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

“…Indeed, previous work showed that vitamin E feeding at the same dose used in our study (2000 I.U. α-tocopherol/kg diet) in female SR-B1 +/− mice increased lipoprotein vitamin E levels [ 39 ]. Further analysis of vitamin E content in HDL particles should be performed in vitamin E supplemented atherogenic diet-fed SR-B1 KO/ApoER61h/h mice to address this issue.…”

Protective Effects of Vitamin E on Heart and Testis Histology Following MDMA (Ecstasy) Exposure in Mice

“…It has been suggested that hyperthermia increases the free radicals formation (24), which results in cardiomyocyte fibrosis (25). However, regarding the preventive effects of vitamin E against ROS and lipid peroxidation (8), the administration of vitamin E in the MDMA + vitamin E group noticeably resulted in testis damage prevention.…”

“…As a fat-soluble non-enzymatic antioxidant, vitamin E has antioxidant activity and intercalates lipids in biological membranes. Therefore, vitamin E isomers can stop ROS-based reactions producing lipid peroxides (8). It is reported that vitamin E deficiency impaired the nervous, skeletal, circulatory, muscular, cardiovascular, immune, and reproductive system (9).…”

Transcriptional profiling of embryos lacking the lipoprotein receptor SR-B1 reveals a regulatory circuit governing a neurodevelopmental or metabolic decision during neural tube closure

“…Instead, SR-B1 is localized in trophoblast giant cells [ 11 , 13 ] surrounding the entire conceptus, that mediate the first step in maternal-fetal nutrient transport. Consistent with SR-B1 localization in cells mediating nutrient uptake, SR-B1 KO embryos show severe vitamin E deficiency [ 12 ]. Interestingly, maternal dietary supplementation with vitamin E completely rescues the NTD phenotype in KO embryos [ 12 ], underscoring the relevance of this vitamin in neural tube closure in this model.…”

“…More recently, we identified the cause of this alteration to be neonatal lethality resultant of neural tube defects (NTD). Between 35 and 50% of SR-B1 KO mouse embryos analyzed in different cohorts failed to close their neural tube in the cranial region, and exhibited exencephaly, a congenital malformation that leads to perinatal death [ 11 , 12 ]. Despite the striking embryonic phenotype observed in SR-B1 KO embryos, SR-B1 protein is not present in the embryo itself during neural tube closure.…”