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

Shan He; Jia He; Siying Ma; Kunyu Wei; Fengchang Wu; Jian Xu; Xiaowei Jin; Yuanhui Zhao; Christopher J Martyniuk

doi:10.1016/j.envint.2024.108747

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

Environ Int. 2024 May 13:188:108747. doi: 10.1016/j.envint.2024.108747. Online ahead of print.

Authors

Shan He¹, Jia He², Siying Ma³, Kunyu Wei³, Fengchang Wu⁴, Jian Xu⁵, Xiaowei Jin⁶, Yuanhui Zhao⁷, Christopher J Martyniuk⁸

Affiliations

¹ College of Geo-exploration Science and Technology, Jilin University, Changchun 130026, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
² Beijing Key Laboratory of Urban Hydrological Cycle and Sponge City Technology, College of Water Sciences, Beijing Normal University, Beijing 100875, China. Electronic address: hejia@bnu.edu.cn.
³ Beijing Key Laboratory of Urban Hydrological Cycle and Sponge City Technology, College of Water Sciences, Beijing Normal University, Beijing 100875, China.
⁴ State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address: wufengchang@vip.skleg.cn.
⁵ State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
⁶ China National Environmental Monitoring Centre, Beijing 100012, China.
⁷ State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin 130117, China.
⁸ Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences, University of Florida, Gainesville, FL 32611, USA.

PMID: 38761427
DOI: 10.1016/j.envint.2024.108747

Abstract

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 in silico 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.

Keywords: Liquid crystal monomer; Molecular docking; T3-related cell-based assay; Thyroid hormone signaling; Visual impairment.