Histopathological changes in the brain of mouse fetuses by etoposide-administration

C. Nam, G.H. Woo, K. Uetsuka, H. Nakayama and K. Doi

Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

Offprint request to: Dr. Chunja Nam, Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. e-mail: vet0215@yahoo.co.kr


Summary. Etoposide (VP-16), a topoisomerase II inhibitor, is an anti-tumor agent which is also known to show embryotoxicity, and teratogenicity when administered to pregnant rodents. We examined VP-16-induced histopathological changes in the brain of mouse fetuses. Pregnant mice were intraperitoneally injected with VP-16 (4 mg/kg) on day 12 of gestation (GD 12), and fetuses were collected from 1 to 48 hours after treatment (HAT). Mitotic neuroepithelial cells in the telencephalic wall prominently decreased at 2 HAT, and were hardly observed at 4 HAT. The number of pyknotic neuroepithelial cells in the fetal brain began to increase at 4 HAT, and became prominent from 8 to 24 HAT. These pyknotic cells were also positively stained by TUNEL method, which can detect fragmented DNA, and showed ultrastructural characteristics of apoptosis. Additionally, these cells were also positive for cleaved caspase-3, an essential executioner of apoptosis. This indicated that excessive neuroepithelial cell apoptosis was induced in the brain of mouse fetuses following VP-16 treatment on GD 12. Histol Histopathol 21, 257-263 (2006)

Key words: Apoptosis, Brain, Etoposide, Fetus, Mouse

DOI: 10.14670/HH-21.257