<br>液晶单体通过甲状腺激素信号破坏斑马鱼幼虫的光感受器图案,Environment International

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液晶单体通过甲状腺激素信号破坏斑马鱼幼虫的光感受器图案
Environment International ( IF 10.3 ) Pub Date : 2024-05-13 , DOI: 10.1016/j.envint.2024.108747
Shan He ₁ , Jia He ₂ , Siying Ma ₂ , Kunyu Wei ₂ , Fengchang Wu ₃ , Jian Xu ₃ , Xiaowei Jin ₄ , Yuanhui Zhao ₅ , Christopher J Martyniuk ₆

Affiliation

液晶单体（LCM）是液晶显示器的原材料，其在电子产品中的使用量正在稳步增加。最近，LCM 被报道为新型内分泌干扰化学物质，然而，其潜在的甲状腺激素干扰和视觉毒性的机制尚不清楚。在这项研究中，选择了六种广泛使用的氟化 LCM (FLCM)，以确定 FLCM 诱导斑马鱼甲状腺和视觉系统毒性的假定机制。暴露于 FLCM 会导致视网膜结构受损，神经节细胞层、内核层和感光层的细胞密度降低约 12.6-46.1%。暴露于 FLCM 还会扰乱甲状腺激素水平，并通过影响斑马鱼幼虫的关键酶和蛋白质来扰乱下丘脑-垂体-甲状腺轴。甲状腺激素依赖性 GH3 细胞活力测定支持了 FLCM 作为甲状腺激素干扰化学物质的假设。还确定，与不含脂肪族环的 FLCM 相比，含有脂肪族环结构的 FLCM 可能具有更高的 T3 拮抗潜力。分子对接表明，FLCM可能影响甲状腺素结合球蛋白、膜受体整合素和甲状腺受体β的生物学功能。最后，暴露于 FLCM 后，斑马鱼在红光和绿光下的视觉运动反应显着受到抑制。综上所述，我们证明 FLCM 可以作为甲状腺激素干扰剂，通过多种分子机制诱导斑马鱼视觉功能障碍。

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Liquid crystal monomers disrupt photoreceptor patterning of zebrafish larvae via thyroid hormone signaling

Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been reported to be novel endocrine disrupting chemicals, however, the mechanisms underlying their potential for thyroid hormone disruption and visual toxicity are not well understood. In this study, six widely used fluorinated LCMs (FLCMs) were selected to determine putative mechanisms underlying FLCM-induced toxicity to the zebrafish thyroid and visual systems. Exposure to FLCMs caused damage to retinal structures and reduced cell density of ganglion cell layer, inner nuclear layer, and photoreceptor layer approximately 12.6–46.1%. Exposure to FLCMs also disrupted thyroid hormone levels and perturbed the hypothalamic-pituitary-thyroid axis by affecting key enzymes and protein in zebrafish larvae. A thyroid hormone-dependent GH3 cell viability assay supported the hypothesis that FLCMs act as thyroid hormone disrupting chemicals. It was also determined that FLCMs containing aliphatic ring structures may have a higher potential for T3 antagonism compared to FLCMs without an aliphatic ring. Molecular docking suggested that FLCMs may affect biological functions of thyroxine binding globulin, membrane receptor integrin, and thyroid receptor beta. Lastly, the visual motor response of zebrafish in red- and green-light was significantly inhibited following exposure to FLCMs. Taken together, we demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms.

更新日期：2024-05-13

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