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Effects on the fetal rat eye of maternal benomyl exposure and protein malnutrition
E R Hoogenboom1, J F Ransdell, W G Ellis
1Department of Nutrition, School of Medicine, University of California, Davis.
Abstract:
Benomyl, a benzimidazole fungicide, produced ocular and craniocerebral malformations in fetal rats when administered to the dams by gavage in a dose of 62.4 mg/kg of maternal body weight/day on days 7-21 of gestation. Ocular anomalies included retinal dysplasia, cataracts, microphthalmia, and anophthalmia. These anomalies occurred in 43.3% of fetuses exposed to benomyl and a normal protein diet but increased to 62.5% when benomyl administration was combined with a protein deficient (8% casein) diet. Microscopic examination of the malformed eyes revealed that the most common abnormality, retinal dysplasia, consisted of rosettes of retinal cells and retinal infolding. The majority of rosettes had a single layer and a limiting membrane. Rosettes with two or three layers were also observed, particularly in fetuses exposed both to protein deficiency and benomyl. Although anophthalmia was identified macroscopically in five fetuses, only a single instance of true anophthalmia was found microscopically. These data support the results of previous investigators that benomyl induces ocular malformation and that protein deficiency enhances the teratogenic effects of benomyl. The disorderly proliferation of retinal cells and rosette formation resembled the periventricular cell masses that accumulate in brains exposed to benomyl and certain other teratogenic agents. The anti-tubulin action of benomyl is known to impair microtubule formation and it may produce brain and ocular malformations by disruption of neuronal proliferation and migration.
Insights
Benomyl fungicide causes eye and brain malformations in fetal rats. Protein deficiency worsens these teratogenic effects, highlighting risks during pregnancy.
Area of Science:
- Toxicology
- Developmental Biology
- Teratology
Background:
- Benzimidazole fungicides, like benomyl, are widely used in agriculture.
- Previous studies suggest potential teratogenic effects of certain fungicides.
- Nutritional status can influence developmental outcomes.
Purpose of the Study:
- To investigate the teratogenic effects of benomyl on fetal development in rats.
- To determine if protein deficiency exacerbates benomyl-induced malformations.
- To elucidate the mechanisms underlying benomyl's teratogenicity.
Main Methods:
- Pregnant rats were administered benomyl via gavage during gestation.
- Different dietary conditions (normal protein vs. protein-deficient) were applied.
- Fetal development, particularly ocular and cranial structures, was assessed macroscopically and microscopically.
Main Results:
- Benomyl exposure caused significant ocular and craniocerebral malformations, including retinal dysplasia, cataracts, microphthalmia, and anophthalmia.
- Protein deficiency combined with benomyl exposure increased the incidence of these malformations.
- Microscopic analysis revealed rosette formation and disorderly retinal cell proliferation.
Conclusions:
- Benomyl is a teratogen that induces ocular and brain malformations in developing rats.
- Protein deficiency significantly enhances the teratogenic effects of benomyl.
- Benomyl's anti-tubulin activity may disrupt neuronal development, leading to malformations.