Developmental hepatotoxicity of liquid crystal monomers in zebrafish: hepatic lipid accumulation and metabolic disruption

Liquid crystal monomers (LCMs), extensively used in electronic display manufacturing, are increasingly detected in environmental and human matrices; however, their potential developmental hepatotoxicity remains poorly understood. In this study, multilevel analyses integrating histopathology, biochemical assays, transcriptomics, qPCR, molecular docking, and transgenic fluorescence imaging were performed to investigate the developmental hepatotoxicity of LCMs in zebrafish larvae. Fluorescence imaging zebrafish demonstrated marked reductions in liver size (40.37%) and fluorescence intensity (16.35%), indicating impaired hepatic organogenesis. Histological and biochemical analyses further revealed aberrant hepatic lipid accumulation, elevated liver injury markers, and oxidative stress responses. Pharmacological inhibition of PPARγ using GW9662 alleviated LCM-induced lipid accumulation and partially restored pparg expression. Mechanistically, excessive lipid accumulation induced by LCM exposure was associated with alterations in PPARγ-related lipid metabolic pathways. Transcriptomic analyses further suggested the involvement of insulin signaling and inflammatory responses, mitochondrial function-related processes, and apoptosis-related signaling pathways. In addition, biochemical and transcriptional alterations consistent with oxidative stress responses and hepatic injury were observed in exposed larvae. Collectively, this study provides integrative evidence that environmentally relevant concentrations of LCMs liver injury, hepatic lipid accumulation, and metabolic disturbances in zebrafish larvae. These findings reveal the developmental hepatotoxicity of LCMs and suggest that LCM-induced disruption of hepatic lipid metabolism may contribute to early metabolic alterations associated with NAFLD. Environmental implication This study highlights that LCM exposure at environmentally relevant concentrations can disrupt hepatic development and lipid metabolism, producing hepatic changes potentially relevant to NAFLD development and raising concerns about their developmental hepatotoxicity. It has significant public health implications, especially as pediatric NAFLD, once thought to affect only adults, now affects approximately 13% of children globally. The condition shows distinct features like fat accumulation and insulin resistance. While lifestyle and genetic factors are known contributors, environmental exposures remain underexplored. The findings suggest that LCMs may perturb hepatic function early in life, with potential implications for later-life liver health, stressing the need for their inclusion in health risk assessments, especially regarding early developmental exposures.