Environmental Toxicology Graduate Program, University of California, Riverside, California, USA.
Department of Environmental Sciences, University of California, Riverside, California, USA.
Environ Toxicol Chem. 2021 Jun;40(6):1586-1595. doi: 10.1002/etc.5002. Epub 2021 Mar 23.
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.
多环芳烃（PAHs）是水生生态系统中普遍存在的污染物，发育中的鱼类胚胎对 PAH 暴露特别敏感。暴露于原油或菲（石油中存在的一种参考 PAH）会在发育中的鱼类胚胎中产生一系列明显的大体形态异常，包括心脏毒性。最近，利用几种暴露于石油的鱼类胚胎的转录组分析研究发现，参与胆固醇生物合成的转录物丰度发生了显著变化。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导致菲诱导的心脏毒性。我们将斑马鱼胚胎暴露于 12 或 15µM 菲从受精后 6 到 72 小时（hpf），并证明与心包水肿和心动过缓一起，胆固醇生物合成途径中的几个基因（fdft1 和 hmgcra）发生了显著改变。当胚胎从 6 到 24 hpf 用胆固醇溶液预处理，然后从 24 到 48 hpf 暴露于菲时，菲对心率的影响部分得到缓解。尽管基因表达发生了变化，但在暴露于菲的胚胎中，胆固醇的全胚胎原位染色并未受到显著影响，其范围从 24 到 72 hpf。然而，在 72 hpf 时，由于菲的暴露，二维卵黄面积显著增加，这表明从卵黄向发育中的胚胎的脂质转运受损。Environ Toxicol Chem 2021;40:1586-1595。©2021 SETAC。
