NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Hunter Biotechnology, Inc., Hangzhou, 310051, China.
Environ Pollut. 2023 Oct 15;335:122260. doi: 10.1016/j.envpol.2023.122260. Epub 2023 Jul 26.
4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 μg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (erα) mRNA, and an interaction between 4-MBC and ERα suggested ERα's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.
4-甲基苄叉樟脑（4-MBC）是一种新兴污染物，作为一种广泛使用的紫外线（UV）过滤器被添加到化妆品中，因为它可以保护皮肤免受紫外线的伤害并抵抗光氧化。尽管 4-MBC 的雌激素活性已得到充分证实，但这种活性与其对神经行为和肝脏的影响之间的联系尚不清楚。因此，我们将斑马鱼幼鱼暴露于环境相关浓度的 4-MBC 中，浓度分别为 3 至 5 天受精后的 1.39、4.17、12.5 和 15.4μg/mL。我们发现，4-MBC 通过增强转基因斑马鱼的荧光产生雌激素效应，这种效应可以通过与雌激素受体拮抗剂共同暴露来拮抗。4-MBC 上调雌激素受体α（erα）mRNA，并且 4-MBC 与 ERα 之间的相互作用表明 ERα 参与了 4-MBC 诱导的雌激素活性。RNA 测序揭示了 4-MBC 在雌激素刺激和脂质代谢中引发的反应。此外，4-MBC 诱导的活动减少和行为表型依赖于雌激素受体（ER）途径。这可能与乙酰胆碱酯酶和乙酰胆碱活性的破坏有关。结果，4-MBC 增加了卵黄蛋白原的表达，并导致斑马鱼幼鱼肝脏中的脂质积累。总的来说，这是第一项报道 4-MBC 通过脑-肝-性腺轴引起雌激素效应的研究。它为 4-MBC 如何干扰大脑和肝脏发育提供了新的见解。
