Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian 361005, China.
Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Sci Total Environ. 2019 May 15;665:995-1002. doi: 10.1016/j.scitotenv.2019.02.154. Epub 2019 Feb 14.
Although Bisphenol F (BPF), a bisphenol A (BPA) analogue with a similar chemical structure to that of BPA, is widely used in commercial products, little is known about its potential toxic effects on the reproductive neuroendocrine system in vivo. The present study aimed to comprehensively evaluate the effects of BPF on the reproductive neuroendocrine system in zebrafish and to assess the potential mechanisms underlying its association with estrogen receptor (ER) and aromatase (AROM) pathways. Long-term exposure to environmentally relevant and low levels of BPF led to increased expression of reproductive neuroendocrine-related genes (kiss1, kiss1r, gnrh3, lhβ, and fshβ) in the zebrafish brain, as well as increased levels of adrenocorticotropic, gonadotropin-releasing, luteinizing, and follicle-stimulating hormones in the zebrafish brain and vitellogenin in the zebrafish liver. In addition, these effects were associated with an increase in erα, erβ, cyp19a, and cyp19b activity. Meanwhile, ER and AROM antagonists, alone or in combination, significantly attenuated the stimulation of kiss1, lhβ, vtg, and gnrh3 expression, thereby suggesting that chronic BPF exposure affects the regulation of the reproductive neuroendocrine system through activation of the ER and AROM pathways. Moreover, since BPF and bisphenol S induced toxic and reproductive neuroendocrine effects similar to those of BPA, the current accepted usage of BPA and its analogs should be reconsidered in the future.
尽管双酚 F（BPF）与双酚 A（BPA）具有相似的化学结构，是 BPA 的一种类似物，被广泛应用于商业产品中，但关于其对体内生殖神经内分泌系统的潜在毒性影响知之甚少。本研究旨在全面评估 BPF 对斑马鱼生殖神经内分泌系统的影响，并评估其与雌激素受体（ER）和芳香酶（AROM）途径相关的潜在机制。长期暴露于环境相关的低浓度 BPF 会导致斑马鱼大脑中生殖神经内分泌相关基因（kiss1、kiss1r、gnrh3、lhβ 和 fshβ）的表达增加，以及大脑中促肾上腺皮质激素、促性腺激素释放激素、促黄体生成素和促卵泡生成素以及肝脏中卵黄蛋白原的水平增加。此外，这些作用与 erα、erβ、cyp19a 和 cyp19b 活性的增加有关。同时，单独或联合使用 ER 和 AROM 拮抗剂可显著减弱 kiss1、lhβ、vtg 和 gnrh3 表达的刺激作用，这表明慢性 BPF 暴露通过激活 ER 和 AROM 途径影响生殖神经内分泌系统的调节。此外，由于 BPF 和双酚 S 引起的毒性和生殖神经内分泌作用与 BPA 相似，未来应重新考虑目前对 BPA 及其类似物的使用。
