EMBRYOTOXICITY OF FUSARIUM MYCOTOXINS, ZEARALENONE AND T-2 TOXIN, IN RATS

The embryotoxicity of the estrogenic mycotoxin, zearalenone (ZEN), and a cytotoxic trichothecene mycotoxin, T-2 toxin (T-2), was investigated in a series of separate experiments. ZEN administered as a single oral dose (50 mg ZEN/kg BW) to 26 mated female rats, during the period of embryonic transport (either 1 or 3 days after mating), completely inhibited embryonic implantation in 18 rats. When examined 12 days after mating, only 2 of the remaining 8 rats had sites of embryonic implantation with morphologically viable embryos. The other 6 rats had sites of embryonic resorption characterized microscopically as deciduomas without embryonic tissue or with embryonic tissue that was retarded in development and degenerate. In an additional 25 pregnant rats similarly treated with ZEN, embryonic transport was accelerated. At least 1 embryo was recovered prematurely from the uterine horns of 18 rats. The number of embryos recovered per rat was diminished indicating that some embryos had been expelled through the vagina. Embryos were not morphologically altered. These findings confirm the estrogenic activity of ZEN in rats, as indicated by altered endometrial responsiveness to embryonic implantation and accelerated embryonic transport. T-2 administered as a single oral dose (2.5 mg/kg BW) to 10 mated female rats, during the period of embryonic organogenesis (11 days after mating), caused complete embryonic resorption in 8 surviving rats examined 5 days after treatment. Eleven of 16 surviving pregnant rats similarly treated but examined 6 to 28 hours after treatment had embryos with multifocal necrosis exemplified by extensive apoptosis of neuroepithelial cells. Two of these rats were moribund and their embryos had diffuse hydropic degeneration indicating hypoxic injury. Although T-2 is directly toxic to rapidly-proliferating cell populations, maternal toxic effects, such as decidual thrombosis, may have contributed secondarily to the embryotoxic effect. Eight surviving pregnant rats treated similarly with a lower dose of T-2 (1.5 mg/kg BW) had partial embryonic resorption, but also had clinical signs and lesions of T-2 intoxication. Fetuses of 5 pregnant rats treated similarly with a nontoxic dose of T-2 (1.0 mg/kg BW) had no morphological evidence of congenital malformation