Hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts sex differentiation of zebrafish (Danio rerio) via an epigenetic mechanism of DNA methylation

IF 4.1 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2024-09-05 DOI:10.1016/j.aquatox.2024.107077

Dan Yang, Fanghua Li, Xiaohui Zhao, Shasha Dong, Guobin Song, Haonan Wang, Xiaoying Li, Guanghui Ding

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引用次数: 0

Abstract

Hexafluoropropylene oxide trimer acid (HFPO-TA), an alternative to perfluorooctanoic acid, has been shown to have estrogenic effects. However, its potential to disrupt fish sex differentiation during gonadal development remains unknown. Therefore, this study exposed zebrafish to HFPO-TA from approximately 2 hours post fertilization (hpf) to 60 days post fertilization (dpf) to investigate its effects on sex differentiation. Results indicated that HFPO-TA disrupted steroid hormone homeostasis, delayed gonadal development in both sexes, and resulted in a female-skewed sex ratio in zebrafish. HFPO-TA exposure up-regulated gene expressions of cyp19a1a, esr1, vtg1 and foxl2, while down-regulated those of amh, sox9a and dmrt1. These suggested that HFPO-TA dysregulated the expressions of key genes related to sex differentiation of zebrafish, promoted the production and activation of estrogen, and further induced the feminization. Interestingly, we observed promoter hypomethylation of cyp19a1a and promoter hypermethylation of amh in male zebrafish, which were negatively associated with their gene expressions. These suggested that HFPO-TA dysregulated these key genes through DNA methylation in their promoters. Therefore, the HFPO-TA disrupted the sex differentiation of zebrafish through an epigenetic mechanism involving DNA methylation, ultimately skewing the sex ratio towards females. Overall, this study demonstrated adverse effects of HFPO-TA on fish sex differentiation and provided novel insights into the underlying epigenetic mechanism.

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六氟环氧丙烷三聚酸（HFPO-TA）通过 DNA 甲基化的表观遗传机制破坏斑马鱼（Danio rerio）的性别分化

六氟环氧丙烷三聚酸（HFPO-TA）是全氟辛酸的替代品，已被证明具有雌激素作用。然而，它在性腺发育过程中破坏鱼类性别分化的潜力仍然未知。因此，本研究将斑马鱼从受精后约 2 小时（hpf）至受精后 60 天（dpf）暴露于 HFPO-TA，以研究其对性别分化的影响。结果表明，HFPO-TA 破坏了类固醇激素的平衡，延缓了雌雄斑马鱼的性腺发育，并导致雌雄斑马鱼的性别比例失调。接触 HFPO-TA 会上调 cyp19a1a、esr1、vtg1 和 foxl2 的基因表达，而下调 amh、sox9a 和 dmrt1 的基因表达。这表明，HFPO-TA 调控了斑马鱼性别分化相关关键基因的表达，促进了雌激素的产生和激活，进一步诱导了斑马鱼的雌性化。有趣的是，我们在雄性斑马鱼中观察到cyp19a1a启动子低甲基化和amh启动子高甲基化，这与它们的基因表达呈负相关。这表明，HFPO-TA 通过启动子中的 DNA 甲基化对这些关键基因进行了失调。因此，HFPO-TA 通过涉及 DNA 甲基化的表观遗传学机制破坏了斑马鱼的性别分化，最终使性别比偏向雌性。总之，这项研究证明了 HFPO-TA 对鱼类性别分化的不利影响，并对其背后的表观遗传机制提供了新的见解。

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来源期刊

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.