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 and , while down-regulated those of and . 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 and promoter hypermethylation of 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.

中文翻译：

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六氟丙烯氧化物三聚酸 (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) 到受精后 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稳态，延迟了两性的性腺发育，并导致斑马鱼的性别比例偏向雌性。 HFPO-TA暴露上调 和 的基因表达，同时下调 和 的基因表达。这表明HFPO-TA失调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，并进一步诱导了雌性化。有趣的是，我们观察到雄性斑马鱼的启动子低甲基化和启动子高甲基化，这与其基因表达呈负相关。这些表明 HFPO-TA 通过启动子中的 DNA 甲基化对这些关键基因进行失调。因此，HFPO-TA通过涉及DNA甲基化的表观遗传机制破坏了斑马鱼的性别分化，最终使性别比例向雌性倾斜。总的来说，这项研究证明了 HFPO-TA 对鱼类性别分化的不利影响，并为潜在的表观遗传机制提供了新的见解。