Vitamin E deficiency disrupts gene expression networks during zebrafish development

Vitamin E (VitE) is essential for vertebrate embryogenesis, but the mechanisms involved remain unknown. To study embryonic development, we fed zebrafish adults (>45 days) either VitE sufficient (E+) or deficient (E–) diets for >80 days, then the fish were spawned to generate E+ and E– embryos. To evaluate the transcriptional basis of the metabolic and phenotypic outcomes, E+ and E– embryos at 12-, 18- and 24 hours post-fertilization (hpf) were subjected to gene expression profiling by RNASeq. Hierarchical clustering, over representation analyses and gene set enrichment analyses were performed with differentially expressed genes. E– embryos experienced overall disruption to gene expression associated with gene transcription, metabolism, intracellular signaling and the formation of embryonic structures. Thus, the apparently moderate changes in lipid peroxidation and metabolic alterations due to VitE deficiency result in major genetic and transcriptional dysregulation as early as 12 hpf, leading to metabolic dysfunction and ultimately lethal outcomes. RNA extracted from whole zebrafish embryos with (E+) and without (E–) Vitamin E at 12, 18 and 24 hours post-fertilization

维生素E（Vitamin E, VitE）是脊椎动物胚胎发生过程中不可或缺的营养物质，但其参与调控的分子机制仍未明确。为研究胚胎发育过程，我们将饲养时长超过45天的成年斑马鱼分别投喂维生素E充足（E+）或缺乏（E–）的饲料达80天以上，随后通过产卵获得E+与E–胚胎。为探究代谢与表型变化的转录调控基础，我们对受精后12、18和24小时（hours post-fertilization, hpf）的E+与E–胚胎开展了RNA测序（RNASeq）基因表达谱分析。基于差异表达基因，我们进行了层级聚类、过度表达富集分析（over representation analyses）以及基因集富集分析。结果显示，E–胚胎的基因表达整体出现紊乱，涉及基因转录、代谢、细胞内信号传导以及胚胎结构形成等相关生物学过程。综上，尽管维生素E缺乏所引发的脂质过氧化与代谢改变仅为轻度变化，但早在受精后12小时（hpf）即可引发严重的遗传与转录调控异常，进而导致代谢功能障碍并最终产生致死结局。本数据集的RNA提取自受精后12、18和24小时的E+与E–斑马鱼全胚。