In recent years, the industrial substitution of long-chain per- and polyfluoroalkyl substances (PFAS) with short-chain alternatives has become increasingly prevalent, resulting in the widespread environmental detection of perfluorohexanesulfonic acid (PFHxS), a short-chain PFAS. However, there remains limited information about the potential adverse effects of PFHxS at environmental concentrations to wildlife. Here, early life stage zebrafish (Danio rerio) were exposed to environmentally relevant concentrations of PFHxS to better characterize the adverse effects of PFHxS on aquatic organisms. Nontargeted, transcriptomic analysis revealed potential hepatotoxic effects in exposed larvae, including macrovesicular and microvesicular hepatic steatosis, as well as focal liver necrosis. Morphological, histological, biochemical, and targeted transcript expression profiles further confirmed significant alterations in hepatocellular lesion numbers, liver pathological structures, relative liver size, liver biochemical parameters, and liver function genes. To validate the PPAR-mediated toxicological mechanism identified as an enriched pathway through in silico bioinformatics analysis, we tested the coexposure to an antagonist and PPAR morpholino knockdown. This intervention alleviated PFHxS-induced hepatic effects, including reductions in the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, and total triglycerides. Our results demonstrate that environmentally relevant concentrations of PFHxS can impair liver development and function in fish, which could have potential risks to aquatic organisms.

中文翻译：

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全氟己烷磺酸 （PFHxS） 通过斑马鱼幼鱼 （Danio rerio） 的 PPAR 信号通路诱导肝毒性


近年来，用短链替代品替代长链全氟烷基和多氟烷基物质 （PFAS） 的工业替代变得越来越普遍，导致短链 PFAS 全氟己烷磺酸 （PFHxS） 的广泛环境检测。然而，关于环境浓度下 PFHxS 对野生动物的潜在不利影响的信息仍然有限。在这里，早期生命阶段的斑马鱼 （Danio rerio） 暴露于环境相关浓度的 PFHxS，以更好地描述 PFHxS 对水生生物的不利影响。非靶向转录组学分析揭示了暴露幼虫的潜在肝毒性作用，包括大泡和微泡肝脂肪变性以及局灶性肝坏死。形态学、组织学、生化和靶向转录物表达谱进一步证实了肝细胞病变数量、肝脏病理结构、肝脏相对大小、肝脏生化参数和肝功能基因的显着改变。为了验证通过计算机生物信息学分析确定为丰富途径的 PPAR 介导的毒理学机制，我们测试了对拮抗剂和 PPAR 吗啉代敲低的共暴露。这种干预减轻了 PFHxS 诱导的肝脏影响，包括降低天冬氨酸转氨酶、丙氨酸转氨酶、总胆固醇和总甘油三酯的水平。我们的结果表明，与环境相关的 PFHxS 浓度会损害鱼类的肝脏发育和功能，这可能对水生生物产生潜在风险。