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  • Title: Developmental toxicity of methanol: Pathogenesis in CD-1 and C57BL/6J mice exposed in whole embryo culture.
    Author: Degitz SJ, Rogers JM, Zucker RM, Hunter ES.
    Journal: Birth Defects Res A Clin Mol Teratol; 2004 Apr; 70(4):179-84. PubMed ID: 15108244.
    Abstract:
    BACKGROUND: Methanol causes axial skeleton and craniofacial defects in both CD-1 and C57BL/6J mice during gastrulation, but C57BL/6J embryos are more severely affected. We evaluated methanol-induced pathogenesis in CD-1 and C57BL/6J embryos exposed during gastrulation in whole embryo culture. METHODS: Conceptuses with five to seven somites were exposed to 0, 1, 2, 3, 4, or 6 mg methanol/ml culture medium for 24 hr and embryonic morphology was assessed. Cell death was evaluated by histology and LysoTracker red staining, and cell-cycle distribution was evaluated by flow cytometry. RESULTS: In C57BL/6J embryos, craniofacial defects were observed at 3 mg methanol/ml and greater. The response for CD-1 embryos was different, with increased dysmorphology only at 6 mg/ml. However, protein content in CD-1 embryos was reduced at 3 mg methanol/ml and above, indicating growth retardation. Yolk sac toxicity occurred only at 6 mg methanol/ml in both strains. Methanol caused only small changes in cell-cycle distribution, while cell death was induced at 4 and 6 mg methanol/ml in both strains after 8 hr. The extent of cell death after 8 hr was greater in C57BL/6J embryos, and increased over time through 18 hr; in contrast, CD-1 embryos showed less cell death at 18 than at 8 hr, suggesting recovery. CONCLUSIONS: Cell death plays a prominent role in methanol-induced dysmorphogenesis, while cell-cycle perturbation may not. Differences in the extent of cell death between CD-1 and C57BL/6J embryos correlated with differences in the severity of dysmorphogenesis.
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