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Maternal sterol 27-hydroxylase is crucial for securing fetal development

GSE247494 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/08/01 Platform GPL19057
Summary
Sterol 27-hydroxylase (Cyp27a1) is a primary enzyme that is involved in the Alternative pathway of bile acid synthesis, which is particularly enhanced during pregnancy. However, the role of this enzyme during fetal organ formation was unclear. Here, we demonstrate that 27-hydroxylase activity in the mother is essential for the progression of pregnancy and organ formation in the fetuses. Maternal depletion of Cyp27a1 reduced success pregnancy rate and litter size. In addition, all of the delivered newborn mice died due to respiratory distress syndrome resulting from the absence of mature alveolar epithelial cells. These phenotypes were caused by 7α-hydroxycholesterol (7α-HC) accumulating in Cyp27a1 deficient mice. Mechanistically, 7α-HC bound to and destabilized a protein Fau, mediating the assembly of ribosomes, the down-regulation of which led to lower protein synthesis and polysome formation. Our study discovered the essential metabolic pathway protecting the developing fetuses from a toxic metabolite.
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Also filed as BioProject PRJNA1038789 and SRA study SRP471278. Searching any of these in the dataset finder brings you back here.

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