Transcriptomic Changes in Zebrafish Embryos and Larvae Following Benzo[a]pyrene Exposure
Transcriptomic Changes in Zebrafish Embryos and Larvae Following Benzo[a]pyrene Exposure
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DOI：
10.1093/toxsci/kfv105
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发表时间：
2015-08-01
影响因子：
3.8
通讯作者：
Willett, Kristine L.
中科院分区：
文献类型：
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作者：
Fang, Xiefan;Corrales, Jone;Willett, Kristine L.
苯并[a]芘(BaP)是一种与环境相关的致癌和内分泌干扰化合物，会导致哺乳动物和鱼类立即、长期和多代的健康缺陷。此前，我们发现BaP改变了斑马鱼发育过程中的DNA甲基化模式，这可能会影响基因的表达。在这里，我们进行了全基因组转录分析，发现在发育中的斑马鱼中存在差异基因表达和剪接。成年斑马鱼暴露于对照组或42.0+/-1.9Mg/L的BaP中，连续7d。在对照条件下采集和饲养卵子，或持续暴露于BaP，直到受精后3.3和96h。对斑马鱼胚胎和仔鱼进行了RNA测序(RNA-Seq)。对数据进行分析以确定差异表达(DE)基因(在基因或转录变异体水平改变)和具有差异外显子使用的基因(DEU；在外显子水平改变)。在3.3HPF时，BaP暴露产生8个DE基因和51个DEU基因。96HPF时，BaP暴露改变了1153个DE基因和159个DEU基因的表达。功能本体论分析表明，许多疾病途径，包括生物死亡、生长障碍、胚胎组织形态异常、先天性心脏病和不利的神经发生，显著丰富了DE和DEU基因，为研究BaP诱导的发育毒性的作用机制提供了新的见解。综上所述，我们发现斑马鱼在发育过程中的基因、转录变异体和外显子水平发生了实质性的转录变化，这些变化可能导致长期的不良生理后果。
Benzo[a]pyrene (BaP) is an environmentally relevant carcinogenic and endocrine disrupting compound that causes immediate, long-term, and multigenerational health deficits in mammals and fish. Previously, we found that BaP alters DNA methylation patterns in developing zebrafish, which may affect gene expression. Herein, we performed a genome-wide transcriptional analysis and discovered differential gene expression and splicing in developing zebrafish. Adult zebrafish were exposed to control or 42.0 +/- 1.9 mu g/l BaP for 7 days. Eggs were collected and raised in control conditions or continuously exposed to BaP until 3.3 and 96h post-fertilization (hpf). RNA sequencing (RNA-Seq) was conducted on zebrafish embryos and larvae. Data were analyzed to identify differentially expressed (DE) genes (changed at the gene or transcript variant level) and genes with differential exon usage (DEU; changed at the exon level). At 3.3 hpf, BaP exposure resulted in 8 DE genes and 51 DEU genes. At 96 hpf, BaP exposure altered expression in 1153 DE genes and 159 DEU genes. Functional ontology analysis by Ingenuity Pathway Analysis revealed that many disease pathways, including organismal death, growth failure, abnormal morphology of embryonic tissue, congenital heart disease, and adverse neuritogenesis, were significantly enriched for the DE and DEU genes, providing novel insights on the mechanisms of action of BaP-induced developmental toxicities. Collectively, we discovered substantial transcriptomic changes at the gene, transcript variant, and exon levels in developing zebrafish after early life BaP waterborne exposure, and these changes may lead to long-term adverse physiological consequences.