Studies on the reproductive effects of Fusarium moniliforme culture material in rats and the biodistribution of [14C] fumonisin B1 in pregnant rats

Abstract

Fumonisins are mycotoxins produced by Fusarium moniliforme and other Fusarium species. They are commonly found in corn and corn-based foodstuffs. Fumonisins inhibit sphingolipid (SL) biosynthesis, alter cellular SL profiles, and thus may affect cell proliferation and differentiation, both of which are important processes for reproduction. However, there are few reports of the effects of F. moniliforme or fumonisins on mammalian reproduction or development. To study the reproductive effects of this fungus, diets formulated with culture material of toxic F. moniliforme strain MRC 826 (CM) to provide 0, 1, 10, or 55 ppm fumonisin B1 (FB1) were fed to male and female rats beginning 9 and 2 weeks before mating, respectively, and continuing throughout mating, gestational, and lactational phases of the study. CM caused nephropathy, typical of FB1, in males fed > or = 10 ppm and females fed 55 ppm FB1. No significant reproductive effects were found in males (n = 12/group), dams, and fetuses examined on gestation day 15 (G15) (n > or = 8/group), or dams and litters through day 21 postpartum (n > or = 9/group). Litter weight gain in the 10 or 55 ppm FB1 groups was slightly decreased; however, gross litter weight and physical development of offspring were not affected. Altered SL ratios indicative of fumonisin exposure, specifically increased sphinganine to sphingosine ratios, were found in the livers of dams from the 55-ppm FB1 group on G15. However, SL ratios of abdominal slices, containing liver and kidney, of fetuses from control and high-dose litters did not differ. In a second experiment, two dams were injected intravenously on G15 with 101 micrograms [14C]FB1 (3.179 x 10(5) dpm). After 1 hr, which allowed for ca. 98% of the dose to be cleared from the maternal blood, negligible amounts of radioactivity were found in the fetuses. Together, these results indicate that the CM, and by inference FB1, did not have significant reproductive effects at doses which are minimally toxic, and further suggest that little in utero FB1 exposure occurred through G15.