Polycyclic aromatic hydrocarbons (PAHs) are pervasive pollutants in aquatic ecosystems, and developing fish embryos are especially sensitive to PAH exposure. Exposure to crude oil or phenanthrene (a reference PAH found in oil) produces an array of gross morphological abnormalities in developing fish embryos, including cardiotoxicity. Recently, studies utilizing transcriptomic analyses in several oil-exposed fish embryos found significant changes in the abundance of transcripts involved in cholesterol biosynthesis. Given the vital role of cholesterol availability in embryonic heart development, we hypothesized that cholesterol dysregulation in early development contributes to phenanthrene-induced cardiotoxicity. We exposed zebrafish embryos to 12 or 15 µM phenanthrene from 6 to 72 h post fertilization (hpf) and demonstrated that, in conjunction with pericardial edema and bradycardia, several genes (fdft1 and hmgcra) in the cholesterol biosynthetic pathway were significantly altered. When embryos were pretreated with a cholesterol solution from 6 to 24 hpf followed by exposure to phenanthrene from 24 to 48 hpf, the effects of phenanthrene on heart rate were partially mitigated. Despite changes in gene expression, whole-mount in situ staining of cholesterol was not significantly affected in embryos exposed to phenanthrene ranging in stage from 24 to 72 hpf. However, the 2-dimensional yolk area was significantly increased with phenanthrene exposure at 72 hpf, suggesting that lipid transport from the yolk to the developing embryo was impaired. Environ Toxicol Chem 2021;40:1586–1595. © 2021 SETAC

中文翻译：

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菲暴露对斑马鱼胚胎胆固醇稳态和心脏毒性的影响

多环芳烃 (PAHs) 是水生生态系统中普遍存在的污染物，发育中的鱼胚胎对 PAH 暴露特别敏感。暴露于原油或菲（油中发现的一种参考 PAH）会在发育中的鱼胚胎中产生一系列严重的形态异常，包括心脏毒性。最近，利用转录组学分析对几个暴露于油的鱼胚胎进行的研究发现，参与胆固醇生物合成的转录本丰度发生了显着变化。鉴于胆固醇可用性在胚胎心脏发育中的重要作用，我们假设早期发育中的胆固醇失调会导致菲诱导的心脏毒性。我们在受精后 6 到 72 小时 (hpf) 将斑马鱼胚胎暴露于 12 或 15 µM 菲，并证明，fdft1和hmgcra ) 在胆固醇生物合成途径中发生了显着改变。当胚胎用 6 到 24 hpf 的胆固醇溶液预处理，然后暴露于 24 到 48 hpf 的菲时，菲对心率的影响会部分减轻。尽管基因表达发生了变化，但在 24 到 72 hpf 阶段暴露于菲的胚胎中，胆固醇的整体原位染色没有显着影响。然而，二维蛋黄面积在 72 hpf 时暴露于菲显着增加，这表明从蛋黄到发育胚胎的脂质转运受损。环境毒物化学2021；40:1586–1595。© 2021 SETAC