Morphological and microarray analysis of T-2 toxin-induced rat fetal brain lesion

Food Chem Toxicol. 2004 Nov;42(11):1727-36. doi: 10.1016/j.fct.2004.06.006.


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.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects*
  • Brain / embryology
  • Brain / pathology
  • DNA Primers
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental / drug effects*
  • HSP70 Heat-Shock Proteins / drug effects
  • HSP70 Heat-Shock Proteins / metabolism
  • Heme Oxygenase (Decyclizing) / drug effects
  • Heme Oxygenase (Decyclizing) / metabolism
  • Immunohistochemistry
  • Kinetics
  • Mitogen-Activated Protein Kinases / drug effects*
  • Mitogen-Activated Protein Kinases / physiology
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / drug effects*
  • Pregnancy
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-2 Toxin / administration & dosage
  • T-2 Toxin / toxicity*
  • Telencephalon / drug effects
  • Telencephalon / embryology


  • DNA Primers
  • HSP70 Heat-Shock Proteins
  • Heme Oxygenase (Decyclizing)
  • Mitogen-Activated Protein Kinases
  • T-2 Toxin