Rapid quantitative high-throughput mouse embryoid body model for embryotoxicity assessment

Quah, Yixian and Jung, Soontag and Ham, Onju and Jeong, Ji-Seong and Kim, Sangyun and Kim, Woojin and Chan, Jireh Yi-Le and Park, Seung-Chun and Lee, Seung-Jin and Yu, Wook-Joon (2024) Rapid quantitative high-throughput mouse embryoid body model for embryotoxicity assessment. Archives of Toxicology, 98 (11). pp. 3897-3908. ISSN 0340-5761, DOI https://doi.org/10.1007/s00204-024-03845-9.

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Abstract

Individuals are exposed to a wide arrays of hazardous chemicals on a daily basis through various routes, many of which have not undergone comprehensive toxicity assessments. While traditional developmental toxicity tests involving pregnant animals are known for their reliability, they are also associated with high costs and time requirements. Consequently, there is an urgent demand for alternative, cost-efficient, and rapid in vitro testing methods. This study aims to address the challenges related to automating and streamlining the screening of early developmental toxicity of chemicals by introducing a mouse embryoid body test (EBT) model in a 384-ultra low attachment well format. Embryoid bodies (EBs) generated in this format were characterized by a spontaneous differentiation trajectory into cardiac mesoderm by as analyzed by RNA-seq. Assessing prediction accuracy using reference compounds suggested in the ICH S5(R3) guideline and prior studies resulted in the establishment of the acceptance criteria and applicability domain of the EBT model. The results indicated an 84.38% accuracy in predicting the developmental toxicity of 23 positive and 9 negative reference compounds, with an optimized cutoff threshold of 750 mu M. Overall, the developed EBT model presents a promising approach for more rapid, high-throughput chemical screening, thereby facilitating well-informed decision-making in environmental management and safety assessments.

Item Type: Article
Funders: Korea Institute of Toxicology [Grant No: KK-2402], Korea Institute of Toxicology, Republic of Korea [Grant No: ARQ202001052004], Ministry of Environment (ME), Republic of Korea
Uncontrolled Keywords: Embryotoxicity; High-throughput screening; Embryoid body; Mouse embryonic stem cells; Accuracy
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology > QR180 Immunology
Divisions: Institute of Advanced Studies
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 Oct 2025 13:11
Last Modified: 13 Oct 2025 13:11
URI: http://eprints.um.edu.my/id/eprint/46518

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