Speaker
Description
In light of bioethics and the principle of the 3Rs (replacement, reduction, and refinement), there is a requirement for reliable platforms to evaluate endocrine-disrupting chemicals (EDCs) in the ecosystem as substitutes for animal testing. However, conventional fish cell cultures have several limitations when compared to primary cells. This study investigates the utilization of a zebrafish liver (ZFL) cell line in three-dimensional (3D) cell culture techniques, including in silico systems in order to develop novel systems for reproductive toxicity assessments. The 3D structure of the zebrafish estrogen receptor was constructed to assess modes of action upon estrogenic chemical exposure. The integration of the structure model and in vitro platforms proved to be valuable tools for screening estrogenic EDCs. Furthermore, 3D ZFL spheroids demonstrated enhanced gene expressions associated with liver functions and higher vitellogenin levels compared to monolayer cells. The 3D spheroid incorporated with nanofibers showed the regulation of intercellular organization and physiological function, addressing the limitations of the spheroid culture. These findings indicate that the engineering of novel 3D platforms shows promise as alternative tools for eco-environmental assessments. Consequently, the current studies have successfully introduced robust alternative platforms to animal and primary cells for the identification of potential EDCs. These approaches contribute to the reduction of animal experimentation in accordance with the 3Rs principle.
References
1) Park, C.G.; Singh N.; Ryu, C.S.; Esterhuizen, M.; Kim, Y.J. Species differences in response to binding interactions of BPA and its analogs with the modeled estrogen receptor 1 and in vitro reporter gene assay in human and zebrafish. Environmental Toxicology and Chemistry 2022, 41(10), 2431–2443. https://doi.org/10.1002/etc.5433
2) Park, C.G.; Jun, I.; Lee, S.; Ryu, C.S.; Lee, S.A.; Park, J.; Han, H.S.; Park, H.; Manz, A.; Shin, H.; Kim, Y.J. Integration of bioinspired fibrous strands with 3D spheroids for environmental hazard monitoring. Small 2022, 18(22), e2200757. https://doi.org/10.1002/smll.202200757
3) Park, C.G.; Ryu, C.S.; Sung, B.; Manz, A.; Kong, H.; Kim, Y.J. Transcriptomic and physiological analysis of endocrine disrupting chemicals Impacts on 3D zebrafish liver cell culture system. Aquat. Toxicol. 2022, 245, 106105. https://doi.org/10.1016/j.aquatox.2022.106105
| Keywords | Endocrine-disrupting chemicals, Zebrafish liver cell, 3D cell culture, Vitellogenin |
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