Publication List English
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/07/09
Quality Control Protocol for Zebrafish Developmental Toxicity Studies
tQuality Control Protocol for Zebrafish Developmental Toxicity Studies
2021/07/09
Quality Control Protocol for Zebrafish Developmental Toxicicological Science
Toshio Tanaka 1, 2, Hajime Kojima 3, Michio Fujiwara 4, Kanako Mori 4, Kyoko Yamamoto 1, 2, Kayoko Yamada 1, 2, Yuka Mizutani 1, 2, Izumi Mori Aoi 1, 2, Yukiko Kato 1, 2
1Systems Pharmacology, Graduate School of Medicine, Mie University
2Medical Zebrafish Research Center, Mie University
3Safety Prediction and Evaluation Division, National Institute of Health Sciences
4Safety Research Institute, Astellas Pharma Inc.
J. Toxicolo. Sci. vol.46 Supplement S239, 2021
On January 29, 2021, PMDA published the DETECTION OF REPRODUCTIVE AND DEVELOPMENTAL TOXICITY FOR HUMAN PHARMACEUTICAL S5(R3) by ICH. And zebrafish developmental toxicity test as an alternative method is now in full swing in Japan. In this study, we have established a zebrafish quality control protocol, which is the most important basis for this zebrafish developmental toxicity test. We found that it was possible to remove these low-quality fertilized eggs, thereby reducing false positive frequency and enhancing the accuracy of zebrafish developmental toxicity testing.
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The most frequently used zebrafish AB line in the world was obtained from ZIRC, USA. We first analyzed 12,919 fertilized eggs and found that 290 eggs (2.3%) had died by 3 hours after fertilization. By 3 hours after fertilization, 290 (2.3%) of the fertilized eggs had died, and 2,055 (16.3%) had morphological abnormalities. By 24 hours after fertilization, 4,646 eggs (36%) were found to be dead. However, the survival rates from 1 to 6 days after fertilization were 64% (1 dpf), 61.3% (2 dpf), and 59.0% (6 dpf), which were stable compared to the rapid decline in survival rate at 24 hours after fertilization. On the other hand, the results of time-lapse imaging at 3 hours to 6 days after fertilization revealed that abnormal egg imaging at 3 hours after fertilization can predict sudden death at least up to 24 hours after fertilization, and diagnostic criteria to enhance the ability to predict death up to 24 hours after fertilization were established. We established diagnostic criteria to enhance the ability to predict mortality up to 24 hours after fertilization. As a result, we report that it was possible to remove these low-quality fertilized eggs prior to the start of compound exposure (6 hpf) for developmental toxicity testing, thereby reducing false positive frequency and enhancing the accuracy of zebrafish developmental toxicity testing.
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The 48th Annual Meeting of the Japanese Society of Toxicology