Developmental effects of fumonisin B1 in mice.
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.
Reddy
R V
RV
Department of Veterinary Biomedical Sciences, University of Missouri, Columbia 65211, USA.
Johnson
G
G
Rottinghaus
G E
GE
Casteel
S W
SW
Reddy
C S
CS
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D037341:Fumonisins; D006849:Hydrocephalus / Q000139:chemically induced; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000196:embryology; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D011247:Pregnancy; D013110:Sphingosine / Q000031:analogs & derivatives / Q000032:analysis
D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D000410:Alanine Transaminase; D013110:Sphingosine; C005682:safingol