Effect in rats of simultaneous prenatal exposure to ochratoxin A and aflatoxin B1. II. Histopathological features of teratological anomalies induced in fetuses

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Abstract
The histopathological features of various abnormalities induced by different doses of ochratoxin A (OA), aflatoxin B1 (AFB1), and their combination in rat fetuses were studied. The pregnant Wistar rats were orally treated during 6–15 gestation days with different doses of OA (0.125, 0.25, 0.50, 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, 1.00 mg/kg), and their combination (0.125+0.125, 0.25+0.50, 0.50+0.25 mg/kg). The fetal sections passing through liver, kidney, brain, heart, and eyes were selected from the fetuses given visceral examination representing each litter. The selected sections were processed for paraffin embedding, stained with H and E, and examined by light microscopy. The histological examination of the fetal organs revealed that OA, AFB1, and their combination treatments caused variable changes in internal organs. In the case of OA, the incidence of pathological lesions liver, kidney, brain, and eye lesions was high, whereas in AFB1treatment, liver, brain, kidney, and heart were affected. The incidence of heart lesions, especially valvular defects, increased in the combination groups. Bile duct proliferation/new bile duct formation, defective ossification of cranial bones, exposure of the brain to the exterior, hypoplasia of cerebellum, and retinal defects observed in OA treatment and spinal cord defects in addition to liver, kidney, and brain changes observed in AFB1 were less severe in the combination groups. The present study indicates that the occurrence of brain, kidney, and liver lesions in combination treatment was less than in either individual treatment suggesting antagonism of OA-induced teratogenic effects by AFB1. The indication of subtle lesions due to an interference with normal development and arrest of differentiation in various internal organs observed in the present study suggests that microscopic examination of the tissues can provide additional useful information to a developmental toxicity study. Birth Defects Res B 71:352–358, 2004.