2. Academic Validation
  3. Zebrafish embryos as a teratogenicity screening tool to reduce potential birth defects

Zebrafish embryos as a teratogenicity screening tool to reduce potential birth defects

  • Reprod Toxicol. 2025 Mar 16:134:108895. doi: 10.1016/j.reprotox.2025.108895.
Zongyu Miao 1,  Jing Yang 2,  Lei Cai 1,  Zhenlie Huang 3,  Erping Yan 4,  Jinghui Peng 5,  Xueping Chen 6,  Jinping Cheng 7
Affiliations

Affiliations

  • 1 Guangdong Provincial Boltechnology Research Institute (Guangdong Provincial Laboratory Animals Monitoring Center), Guangzhou 510663, China.
  • 2 Department of Science and Environmental Studies and State Key Laboratory of Marine Pollution, The Education University of Hong Kong, New Territories, Hong Kong SAR, China.
  • 3 NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 4 Kangaroo Mommy Research Centre, Guangdong Kangaroo Mommy Biotechnology Co. Ltd, China.
  • 5 Centre for Biotech Big Data Research & Development, Research Institute of Tsinghua, Pearl River Delta, China; Vitargent (International) Biotechnology Limited, Unit 516, 5/F. Biotech Centre 2, No. 11 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong SAR, China.
  • 6 Centre for Biotech Big Data Research & Development, Research Institute of Tsinghua, Pearl River Delta, China; Vitargent (International) Biotechnology Limited, Unit 516, 5/F. Biotech Centre 2, No. 11 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong SAR, China. Electronic address: xueping.chen@vitargent.com.
  • 7 Department of Science and Environmental Studies and State Key Laboratory of Marine Pollution, The Education University of Hong Kong, New Territories, Hong Kong SAR, China; The Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, Guangdong, China. Electronic address: jincheng@eduhk.hk.
PMID: 40097051 DOI: 10.1016/j.reprotox.2025.108895
Abstract

Teratogens play a crucial role in the development of birth defects, making effective screening vital for prevention and management. This study aimed to develop an optimized zebrafish embryo-based platform for teratogenicity screening and further evaluate its findings with established clinical and animal data. Zebrafish embryos [6-8 h post-fertilization (hpf)] were exposed to 19 different test solutions, including nine known teratogens and ten non-teratogens, in 96-well plates, and mortality and morphological abnormalities were assessed at 48, 72, and 96 hpf. The half-lethal concentration (LC50) and half-effective concentration (EC50) were calculated from the counts of dead and abnormal embryos, respectively. The teratogenicity index (TI), defined as LC50/EC50, was used to classify the chemicals. Of the tested compounds, eight were identified as teratogenic, nine as non-teratogenic, and two outliers due to solubility constraints in this assessment. Notably, extending the exposure duration to 96 hpf provided a more accurate assessment of teratogenicity compared to shorter exposures. Eight teratogenic substances exhibited a TI greater than 3, while (-)-thalidomide did not yield a definitive TI due to low solubility. Among the non-teratogenic chemicals, nine had a TI below 3, with ajmaline also lacking a precise TI due to solubility constraints. These findings suggest that using a 6-8 hpf to 96 hpf exposure window and establishing a TI threshold of 3 can facilitate reliable teratogenicity risk assessment. Furthermore, the phenotypes observed in zebrafish embryos were consistent with typical teratogenic malformations documented in clinical and animal studies. This study demonstrates that the refined zebrafish embryo teratogenicity testing method coupled with the TI, can be an effective tool for assessing teratogenic risk.

Keywords

Birth defect; Malformation; Teratogenicity; Teratogenicity index; Zebrafish embryo.

Figures
Products