T-2 toxin (2 mg/kg b.w.) was orally inoculated to pregnant mice at gestational day (GD) 8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, 15.5 and GD 16.5, respectively, and the fetuses were examined 24 hours later. The number and region of pyknotic or karyorrhectic cells varied according to inoculation date. In the GD 13.5-subgroup, a moderate to high number of pyknotic or karyorrhectic neuronal cells were observed in the central nervous system, peri-ventricular zone to subventricular zone, and pyknosis or karyorrhexis were also observed in a small number of chondroblasts and chondrocytes. In the GD 16.5-subgroup, a moderate to high number of pyknotic or karyorrhectic cells were observed in the thymus and renal subcapsular parenchyma. The nuclei of these pyknotic or karyorrhectic cells were strongly stained by the terminal deoxy nucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling method widely used for the in situ detection of apoptotic nuclei. In addition, a few fetuses from darns which were given T-2 toxin at GD 13.5 or GD 14.5 and killed at GD 17.5 showed skeletal abnormalities such as wavy ribs and short scapula. From the present findings and the well known fact that T-2 toxin readily crosses the rat placenta, it seems that T-2 toxin-induced apoptosis in the developing mouse fetuses might be a direct effect of T-2 toxin on fetuses.
