Effect of Methotrexate on Neuroepithelium in the Rat FetalBrain

Journal of Veterinary Medical Science

Shota INOUE²  Jing SUN²  Satoshi FURUKAWA¹  Takashi TAKEUCHI²  Akihiko SUGIYAMA² 

[1] Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349�?0294, Japan;Courses of Veterinary Laboratory Medicine, School of Veterinary Medicine, Faculty of Agriculture, Tottori University, 4�?101 Koyama-cho Minami, Tottori, Tottori 680�?8553, Japan

关键词: apoptosis;    brain;    fetus;    methotrexate;    neuroepithelial cell;   

DOI  :  10.1292/jvms.13-0457

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(44)Cited-By(2)Pregnant rats were treated with 30 mg/kg of methotrexate (MTX) on gestation day13, and fetal brains were examined histopathologically from 6 to 48 hr after thetreatment. In the telencephalon of the control group, there were few pyknoticneuroepithelial cells throughout the experimental period. Six hr after MTX treatment,several pyknotic neuroepithelial cells scattered throughout the telencephalic wall. At12�?36 hr, pyknotic neuroepithelial cells increased significantly and were diffuselydistributed throughout the telencephalic wall. Neuroepithelial cells were eliminated andshowed sparse cell density at 36 hr in the telencephalon. Almost all fetuses died at 48hr. Most of the pyknotic neuroepithelial cells were positively stained by the TUNEL methodand positive for cleaved caspase-3. While mitotic and phospho-histone H3-positiveneuroepithelial cells were located along the ventricular layer of telencephalon in thecontrol group, they were rarely observed in the same region at 6�?36 hr in the MTX-treatedgroup. MTX induced few pyknotic changes to neuroepithelial cells in the metencephalon,compared to other parts of brain. The distribution of apoptotic neuroepithelial cells andthe time-course changes of the indices of apoptotic and mitotic neuroepithelial cells weredifferent from those of other DNA-damaging chemicals reported previously. The differencemay reflect the disparity in mechanisms of apoptosis and the inhibition of cellproliferation in neuroepithelial cells induced by MTX. To our knowledge, this is the firstreport demonstrating histopathological findings of fetal brain damage induced by MTX.

【 授权许可】

Unknown