The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. Previous research in zebrafish (Danio rerio) has shown that 0.2 μM exposures to 4-PCB-11-Sulfate starting at 1 day post fertilization (dpf) increase hepatic neutral lipid accumulation in larvae at 15 dpf. Here, we explored whether nuclear factor erythroid 2-related factor 2 (Nrf2), known as the master-regulator of the adaptive response to oxidative stress, contributes to metabolic impacts of 4-PCB-11-Sulfate. For this work, embryos were collected from homozygous wildtype or Nrf2a mutant adult zebrafish that also express GFP in pancreatic β-cells, rendering Tg(ins:GFP;nrf2a^fh318+/+) and Tg(ins:GFP;nrf2a^fh318-/−) lines. Exposures were conducted from 1-15 dpf to either 0.05% DMSO or DMSO-matched 0.2 µM 4-PCB-11-Sulfate, and at 15 dpf subsets of larvae were imaged for overall morphology, primary pancreatic islet area, and collected for fatty acid profiling and RNAseq. At 15 dpf, independent of genotype, fish exposed to 4-PCB-11-Sulfate survived significantly more at 80–85% compared to 65–73% survival for unexposed fish, and had primary pancreatic islets 8% larger compared to unexposed fish. Fish growth at 15 dpf was dependent on genotype, with Nrf2a mutant fish a significant 3–5% shorter than wildtype fish, and an interaction effect was observed where Nrf2a mutant fish exposed to 4-PCB-11-Sulfate experienced a significant 29% decrease in the omega-3 fatty acid DHA compared to unexposed mutant fish. RNAseq revealed 308 differentially expressed genes, most of which were dependent on genotype. These findings suggest that Nrf2a plays an important role in growth as well as for DHA production in the presence of 4-PCB-11-Sulfate. Further research would be beneficial to understand the importance of Nrf2a throughout the lifecourse, especially in the context of toxicant exposures.

环境污染物 3,3'-二氯联苯 (PCB-11) 是一种低氯多氯联苯 (PCB) 同系物，存在于空气和水样中。PCB-11 及其代谢物 4-PCB-11-Sulfate 在人类（包括孕妇）中均有检测到。以前对斑马鱼的研究（斑马鱼) 表明，从受精后 1 天 (dpf) 开始，0.2 μM 暴露于 4-PCB-11-Sulfate 会增加 15 dpf 幼虫的肝脏中性脂质积累。在这里，我们探讨了核因子红细胞 2 相关因子 2 (Nrf2)，被称为对氧化应激的适应性反应的主要调节因子，是否有助于 4-PCB-11-硫酸盐的代谢影响。对于这项工作，胚胎是从纯合子野生型或 Nrf2a 突变体成年斑马鱼中收集的，这些斑马鱼也在胰腺 β 细胞中表达 GFP，呈现 Tg（ins：GFP；nrf2a ^fh318+/+）和Tg（ins：GFP；nrf2a ^fh318-/-）线。曝光从 1-15 dpf 到 0.05% DMSO 或 DMSO 匹配的 0.2 µM 4-PCB-11-硫酸盐，并在 15 dpf 对幼虫子集进行整体形态成像、原发性胰岛面积，并收集脂肪酸分析和 RNAseq。在 15 dpf 时，与基因型无关，暴露于 4-PCB-11-硫酸盐的鱼的存活率显着高于未暴露鱼的 65-73%，而暴露于 4-PCB-11-硫酸盐的鱼的存活率为 65-73%，并且与未暴露的鱼相比，原代胰岛大 8%。鱼在 15 dpf 的生长取决于基因型，Nrf2a 突变鱼比野生型鱼短 3-5%，并且观察到相互作用效应，其中暴露于 4-PCB-11-硫酸盐的 Nrf2a 突变鱼经历了 29% 的显着减少与未暴露的突变鱼相比，在 omega-3 脂肪酸 DHA 中。RNAseq 揭示了 308 个差异表达基因，其中大部分取决于基因型。这些发现表明，在 4-PCB-11-Sulfate 存在的情况下，Nrf2a 在生长以及 DHA 生产中起着重要作用。进一步的研究将有助于了解 Nrf2a 在整个生命过程中的重要性，尤其是在接触有毒物质的情况下。