Lipid Remodeling in Mouse SR-B1-Deficient Embryos with Oxidative Stress-Associated Neural Tube Defects

Neural tube defects (NTD) are congenital malformations that lead to structural abnormalities of the brain or spine. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1 KO), the main receptor for high-density lipoproteins, exhibit a high incidence of anterior NTD, which is associated with vitamin E deficiency and elevated levels of reactive oxygen species (ROS). Maternal supplementation with vitamin E, a micronutrient with antioxidant properties, completely prevents the occurrence of NTD and normalizes ROS levels in SR-B1 KO embryos, suggesting a contribution of oxidative stress to NTD in this model. In this work, we showed that SR-B1 KO embryos at gestational day E9.5 display higher levels of lipoperoxidative damage markers. Analysis of data obtained through shotgun lipidomics evidenced a selective and coordinated reorganization of fatty acid distribution, characterized by altered polyunsaturated and monounsaturated composition, together with reduced phosphatidylcholine and increased lysophosphatidylcholine levels, and diversion of fatty acids into triacylglyceride storage. Transcriptomic analysis revealed a coordinated upregulation of genes involved in phospholipid synthesis and remodeling, consistent with the altered lipid homeostasis observed in SR-B1 KO embryos. Together, these results provide novel information showing a potential link between oxidative stress and disruptions in mammalian embryonic lipid metabolism, highlighting phospholipid remodeling as a potential determinant of susceptibility to NTD.