4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae

作者：Xian, Hongyi; Li, Zhiming; Ye, Rongyi; Dai, Mingzhu; Feng, Yu; Bai, Ruobing; Guo, Jie; Yan, Xiliang; Yang, Xingfen; Chen, Da; Huang, Zhenlie^*

来源：Environmental Pollution, 2023, 335: 122260.

DOI：10.1016/j.envpol.2023.122260

• 4-Methylbenzylidene camphor
• Emerging contaminant
• Estrogenic activity
• Hypoactivity
• Lipid accumulation
• Brain -liver -gonad axis

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 4MBC with 1.39, 4.17, 12.5 and 15.4 & mu;g/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 (er & alpha;) mRNA, and an interaction between 4-MBC and ER & alpha; suggested ER & alpha;& PRIME;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.

• 单位
  广州大学; 南方医科大学