title: Morphological and microarray analysis of T-2 toxin-induced rat fetal brain lesion.
abstract: To examine morphological and gene expression changes induced by T-2 toxin in the fetal brain in detail, pregnant rats on day 13 of gestation were treated orally with a single dose of T-2 toxin (2 mg/kg) and sacrificed at 1, 3, 6, 9, 12 and 24 h after treatment (HAT). Histopathologically, the number of apoptotic neuroepithelial cells in the telencephalon increased from 1 HAT and peaked at 12 HAT. Based on the histopathological examinations, microarray analysis was performed at 6, 12 and 24 HAT. Microarray analysis showed that the expression of oxidative stress-related genes (heat shock protein 70 (HSP70) and heme oxygenase (HO)) was strongly induced by T-2 toxin at 12 HAT, the peak time point of apoptosis induction. The expression of mitogen-activated protein kinase (MAPK)-related genes (MEKK1 and c-jun) and other apoptosis-related genes (caspase-2 and insulin-like growth factor-binding protein-3 (IGF-BP3)) was also induced by the T-2 toxin treatment. The changes observed by microarray analysis were confirmed for four up-regulated genes (HSP70, HO, IGF-BP3 and VEGF-A) using real-time RT-PCR. Our results suggest that the T-2 toxin-induced apoptosis in the fetal brain is due to oxidative stress, and that the MAPK pathway may be involved in T-2 toxin-induced toxicity.
authors.affiliation: 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. sehata@sankyo.co.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Sehata
authors.forename: Naoki
authors.initials: N
authors.lastname: Kiyosawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Makino
authors.forename: Fusako
authors.initials: F
authors.lastname: Atsumi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamoto
authors.forename: Munehiro
authors.initials: M
authors.lastname: Teranishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Baba
authors.forename: Koji
authors.initials: K
authors.lastname: Uetsuka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013605:T-2 Toxin / Q000008:administration & dosage / Q000633:toxicity*; D013687:Telencephalon / Q000187:drug effects / Q000196:embryology
chemical_list: D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing); D020928:Mitogen-Activated Protein Kinases; D013605:T-2 Toxin