Rericha Yvonne, St Mary Lindsey, Truong Lisa, McClure Ryan, Martin J Kainalu, Leonard Scott W, Thunga Preethi, Simonich Michael T, Waters Katrina M, Field Jennifer A, Tanguay Robyn L
Environmental and Molecular Toxicology Department, College of Agricultural Sciences, Oregon State University, Corvallis, OR, United States.
Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR, United States.
Front Toxicol. 2024 Jul 22;6:1425537. doi: 10.3389/ftox.2024.1425537. eCollection 2024.
Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity. In the present study, we prioritized 15 bioactive PFAS that induced significant morphological effects and performed RNA-sequencing to characterize early transcriptional responses at a single timepoint (48 h post fertilization) after early developmental exposures (8 h post fertilization). Internal concentrations of 5 of the 15 PFAS were measured from pooled whole fish samples across multiple timepoints between 24-120 h post fertilization, and additional temporal transcriptomics at several timepoints (48-96 h post fertilization) were conducted for Nafion byproduct 2. A broad range of differentially expressed gene counts were identified across the PFAS exposures. Most PFAS that elicited robust transcriptomic changes affected biological processes of the brain and nervous system development. While PFAS disrupted unique processes, we also found that similarities in some functional head groups of PFAS were associated with the disruption in expression of similar gene sets. Body burdens after early developmental exposures to select sulfonic acid PFAS, including Nafion byproduct 2, increased from the 24-96 h post fertilization sampling timepoints and were greater than those of sulfonamide PFAS of similar chain lengths. In parallel, the Nafion byproduct 2-induced transcriptional responses increased between 48 and 96 h post fertilization. PFAS characteristics based on toxicity, transcriptomic effects, and modes of action will contribute to further prioritization of PFAS structures for testing and informed hazard assessment.
全氟和多氟烷基物质（PFAS）是一类广泛存在且持久的污染物，对环境和人类健康构成重大威胁。目前，人们对结构多样的PFAS毒性作用机制的全面了解还很欠缺。为满足这一需求，我们最近报道了利用斑马鱼评估大量PFAS发育毒性的应用。在本研究中，我们对15种具有显著形态学效应的生物活性PFAS进行了优先排序，并进行了RNA测序，以表征早期发育暴露（受精后8小时）后单个时间点（受精后48小时）的早期转录反应。在受精后24 - 120小时的多个时间点，从合并的全鱼样本中测量了15种PFAS中5种的体内浓度，并对Nafion副产物2在几个时间点（受精后48 - 96小时）进行了额外的时间转录组学研究。在PFAS暴露中发现了广泛的差异表达基因计数。大多数引起强烈转录组变化的PFAS影响了大脑和神经系统发育的生物学过程。虽然PFAS破坏了独特的过程，但我们也发现，PFAS某些功能头基的相似性与相似基因集表达的破坏有关。早期发育暴露于选定的磺酸PFAS（包括Nafion副产物2）后的体内负荷在受精后24 - 96小时采样时间点增加，且高于类似链长的磺酰胺PFAS。同时，Nafion副产物２诱导的转录反应在受精后48至96小时增加。基于毒性、转录组效应和作用模式的PFAS特征将有助于进一步对PFAS结构进行优先排序，以进行测试和明智的危害评估。
