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Developmental effects of fumonisin B1 in mice
R V Reddy1, G Johnson, G E Rottinghaus
1Department of Veterinary Biomedical Sciences, University of Missouri, Columbia 65211, USA.
Abstract:
Developmental and toxic effects of aqueous extracts of F. moniliforme culture material containing known levels of fumonisin B1 were recently reported in mice and included maternal hepatotoxicity and lethality, maternal body weight gain reduction, increased embryonic resorptions, reduced offspring body weights, and fetal malformations including cleft palate, hydrocephalus, malformed ribs and incomplete digital and sternal ossification. These studies also suggested that the effects of the fungal extract on the mouse offspring may be mediated via maternal effects. The contribution of fumonisin B1 (FB1), a major toxic metabolite of F. moniliforme, in the induction of these effects was evaluated in this study by administering 0 to 100 mg pure FB1/kg of body weight on gestational days (GD) 7 through 15 to pregnant Charles River CD1 mice and assessing maternal health and fetal development till the end of gestation. Doses of 25 mg/kg or higher of pure FB1 induced maternal liver lesions (mostly necrotic changes), associated with ascites and increased hepatocytic nuclear diameter. Fumonisin doses of 50 mg/kg or higher also resulted in significantly increased maternal ALT on GD12, and reduced offspring bodyweights on GD18. Increased resorptions and decreased numbers of live offspring were only evident at 100 mg FB1/kg body weight. Offspring exhibited dose-dependent increase in the incidence and severity of hydrocephalus of both the lateral and third ventricles at doses of 25 mg/kg or higher. Doses of 25 mg/kg or higher also increased the sphinganine/sphingosine (Sa/So) ratios in maternal but not fetal livers. These results suggest that FB1 may be a developmental toxicant accounting for most but not all earlier reported effects of F. moniliforme culture extract. Association of FB1 effects on the offspring with maternal hepatoxicity and with alteration of Sa/So ratio in maternal but not fetal liver supported the earlier claim that FB1 effects on the mouse offspring are mediated by maternal hepatotoxicity.
Insights
Fumonisin B1 (FB1), a fungal toxin, caused maternal liver damage and fetal abnormalities like hydrocephalus in mice. These developmental effects appear to be linked to maternal toxicity, suggesting FB1 is a significant developmental toxicant.
Area of Science:
- Toxicology
- Developmental Biology
- Mycotoxicology
Background:
- Fungal extracts of F. moniliforme cause developmental toxicity in mice.
- Fumonisin B1 (FB1) is a major toxic metabolite of F. moniliforme.
- Previous studies suggested maternal effects mediate offspring toxicity.
Purpose of the Study:
- To evaluate the contribution of pure FB1 to the developmental and toxic effects observed with F. moniliforme extracts.
- To determine dose-dependent effects of FB1 on maternal health and fetal development in mice.
Main Methods:
- Pregnant mice were administered 0-100 mg/kg pure FB1 from gestational days 7-15.
- Maternal health (liver lesions, ALT levels) and fetal development (body weight, malformations, ossification) were assessed.
- Sphinganine/sphingosine (Sa/So) ratios in maternal and fetal livers were analyzed.
Main Results:
- FB1 doses ≥25 mg/kg caused maternal liver lesions and increased Sa/So ratios in maternal livers.
- Doses ≥50 mg/kg increased maternal ALT and reduced offspring body weight.
- Hydrocephalus and increased resorptions were observed at higher FB1 doses (≥25 and 100 mg/kg, respectively).
Conclusions:
- FB1 is a developmental toxicant responsible for most, but not all, effects of F. moniliforme extract.
- Maternal hepatotoxicity and altered Sa/So ratios in maternal liver likely mediate FB1's effects on offspring development.
- FB1 poses a significant risk during pregnancy, necessitating careful monitoring of exposure.