Effect of methotrexate exposure at late gestation on development of telencephalon in rat fetal brain

Journal of Veterinary Medical Science

Satoshi FURUKAWA²  Takashi TAKEUCHI¹  Ayano HIRAKO¹  Akihiko SUGIYAMA¹ 

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

关键词: apoptosis;    brain;    fetus;    methotrexate;    neuronal migration disorder;   

DOI  :  10.1292/jvms.15-0389

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(55)Pregnant rats were treated with 30 mg/kg of methotrexate (MTX) on gestation day (GD) 16, and fetal brains were examined time-dependently. On GD 20, the appearance of the telencephalon in the MTX group was different from that in the control group, and the major axis of the telencephalon of the MTX group was shortened, compared to that of the control group. In the sagittal section of the telencephalon in the MTX group on GD 20, histopathological findings of deformation and narrowing of the cerebral ventricle, the disturbance of the arrangement of the marginal cell layer of subventricular zone (SVZ) and thickening of telencephalic wall, cortical plate and ventricular zone (VZ)/SVZ were possibly attributable to neuronal migration disorders by MTX. Through all the experimental period, few pyknotic cells or TUNEL-positive cells were observed in the VZ/SVZ of the telencephalic wall and striatum in the control group. On the other hand, in the VZ/SVZ of the telencephalic wall and striatum in the MTX group, pyknotic cells or TUNEL-positive cells were observed on GD 17, and they increased significantly on GD18 and then decreased to the control levels from GD 19 onward. The phospho-Histone H3-positive rate decreased remarkedly in the VZ/SVZ of the telencephalic wall and striatum of the MTX group on GDs 17 and 18, compared to the control group, but they recovered on and after GD 19. These results suggested that there was a high possibility that development of the telencephalon in this period required strong folic acid.

【 授权许可】

Unknown