College of Environmental Science and Engineering, Dalian Maritime University, Dalian 116026, China.
College of Environmental Science and Engineering, Dalian Maritime University, Dalian 116026, China.
Aquat Toxicol. 2024 Oct;275:107077. doi: 10.1016/j.aquatox.2024.107077. Epub 2024 Sep 5.
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.
六氟环氧丙烷三氟乙酸酯（HFPO-TA）是全氟辛酸（PFOA）的替代品，具有雌激素效应。然而，其在鱼类性腺发育过程中对性别分化的潜在干扰作用尚不清楚。因此，本研究从受精后约 2 小时（hpf）到受精后 60 天（dpf）暴露于 HFPO-TA 中，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动态平衡，延迟了雌雄两性的性腺发育，并导致斑马鱼出现雌性偏斜的性别比例。HFPO-TA 暴露上调了 cyp19a1a、esr1、vtg1 和 foxl2 的基因表达，而下调了 amh、sox9a 和 dmrt1 的基因表达。这表明 HFPO-TA 扰乱了与斑马鱼性别分化相关的关键基因的表达，促进了雌激素的产生和激活，进而诱导了雌性化。有趣的是，我们观察到雄性斑马鱼中 cyp19a1a 的启动子低甲基化和 amh 的启动子高甲基化，与它们的基因表达呈负相关。这表明 HFPO-TA 通过其启动子中的 DNA 甲基化来扰乱这些关键基因。因此，HFPO-TA 通过涉及 DNA 甲基化的表观遗传机制扰乱了斑马鱼的性别分化，最终导致雌性偏斜的性别比例。总之，本研究表明 HFPO-TA 对鱼类性别分化具有不利影响，并为潜在的表观遗传机制提供了新的见解。
