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

Yixian Quah1, Soontag Jung1, Onju Ham1

  • 1Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea.

Archives of Toxicology
|September 5, 2024
PubMed
Summary

A new mouse embryoid body test (EBT) offers rapid, cost-efficient screening for chemical developmental toxicity. This in vitro model accurately predicts hazardous chemical effects, aiding environmental safety assessments.

Keywords:
AccuracyEmbryoid bodyEmbryotoxicityHigh-throughput screeningMouse embryonic stem cells

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Area of Science:

  • Toxicology
  • Developmental Biology
  • In vitro testing

Background:

  • Chemicals pose daily risks, yet many lack toxicity data.
  • Traditional animal tests for developmental toxicity are costly and slow.
  • There's a need for faster, cheaper in vitro alternatives.

Purpose of the Study:

  • To develop and validate a high-throughput in vitro model for early developmental toxicity screening.
  • To automate and streamline the assessment of chemical hazards.
  • To establish criteria for the reliable application of the new test.

Main Methods:

  • Utilized a mouse embryoid body test (EBT) in a 384-ultra low attachment well format.
  • Characterized embryoid body differentiation using RNA sequencing.
  • Validated the EBT model with 32 reference compounds (23 positive, 9 negative) from ICH S5(R3) and prior studies.

Main Results:

  • The EBT model demonstrated spontaneous differentiation into cardiac mesoderm.
  • An optimized cutoff threshold of 750 µM was established.
  • The model achieved 84.38% accuracy in predicting developmental toxicity for reference compounds.

Conclusions:

  • The developed EBT model is a promising tool for rapid, high-throughput chemical screening.
  • This method facilitates informed decision-making in environmental management and chemical safety.
  • The EBT model addresses the demand for efficient in vitro developmental toxicity testing.