Title of Research:
23-1-03
Development of an alternative method for teratogenicity using zebrafish
Principal Investigator:
Hiromi Hirata, PhD (Professor, Department of Chemistry and Biological Science, College of
Science and Engineering, Aoyama Gakuin University)
5-10-1 Fuchinobe, Sagamihara 252-5258, Japan(tel) 042-759-6235 (email) hihirata@chem.aoyama.ac.jp
Collaborators:
Kota Ujibe, MSc (Graduate Student, Aoyama Gakuin University)
Kenichiro Sadamitsu, MSc (Graduate Student, Aoyama Gakuin University)
Chitose Taya (Research Technician, Aoyama Gakuin University)
Makoto Kashima (Lecturer, Toho University)
Junichi Tasaki (Senior Scientist, Safety Science Research, Kao Corporation)
Shujie Liu (Scientist, Safety Science Research, Kao Corporation)
Summary of Research:
We performed whole genome sequencing of 15 zebrafish strains including AB, TU, RW and WIK
and determined genetic tree. We used these strains for developmental toxicity tests and found that
there were no strain difference of susceptibility to chemicals. In addition to teratogenicity, which isevaluated by appearance, gene expression changes by RNA-Seq were also examined as ahazard identification. We confirmed that the differences by strains were smaller than thedifferences by exposure concentration. These results suggest that it is not necessary to use
specific strain when conducting developmental toxicity tests using zebrafish and that any strain
can be used in the tests. We also found a correlation between changes in gene expression andteratogenicity that could explain the characteristics of teratogenicity. This suggests the possibilityof using gene expression changes by RNA-Seq as a useful strategy to identify the AOP ofdevelopmental toxicity.
Timeline:
March 1, 2023 Topics:
1. "Development of an alternative method for teratogenicity using zebrafish" at the 2023 LRIResearch report meeting of the Japan Chemical Industry Association. August 25, 2023.
Publications:
1. Kenichiro Sadamitsu, Fabien Velilla, Minori Shinya, Makoto Kashima, Yukiko Imai, Toshihiro
Kawasaki, Kenta Watai, Miho Hosaka, Hiromi Hirata and Noriyoshi Sakai. Establishment of azebrafish inbred strain, M-AB, capable of regular breeding and genetic manipulation. ScientificReports. (Under revision)
2. Hiromi Hirata. Investigation of strains in toxicity testing of chemicals using zebrafish. Japan
Pharmaceutical Manufacturers Association "Current status of alternative methods forreproductive and developmental toxicity" Symposium. Nihonbashi life science building, Tokyo.
February 8, 2024. (Invited symposium speaker)
3. Kota Ujibe, Makoto Kashima, Rintaro Shimada, Masanari Okamoto, Seiji Wada, Hiroki
Matsuda, Akira Sakamoto and Hiromi Hirata. Zebrafish lacking Werner syndrome gene wrn
cause early nutritional deficiency. The 9th Zebrafish and Medaka-based Drug Discovery
Meeting. MEXT research exchange center, Tsukuba. November 6, 2023. (Oral presentation)
4. Kenichiro Sadamitsu, Minori Shinya, Makoto Kashima, Noriyoshi Sakai and Hiromi Hirata.
Establishment and whole genome analysis of zebrafish inbred strain M-AB," The 96th Annual
Meeting of the Japanese Biochemical Society. Fukuoka International Conference Hall,Fukuoka. November 1, 2023. (Poster presentation)