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DEVELOPMENTAL TOXICITY OF METHANOL: PATHOGENESIS IN CD-1 AND C57BL/6J MICE EXPOSED IN WHOLE EMBRYO CULTURE
Citation:
Degitz, S J., J M. Rogers, R M. Zucker, AND E S. Hunter III. DEVELOPMENTAL TOXICITY OF METHANOL: PATHOGENESIS IN CD-1 AND C57BL/6J MICE EXPOSED IN WHOLE EMBRYO CULTURE. BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 70(4):179-184, (2004).
Impact/Purpose:
To evaluate methanol-induced pathogenesis in mouse embryos
Description:
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.