Developmental toxicity of methanol: Pathogenesis in CD-1 and C57BL/6J mice exposed in whole embryo culture
✍ Scribed by Sigmund J. Degitz; John M. Rogers; Robert M. Zucker; E. Sidney Hunter III
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 247 KB
- Volume
- 70
- Category
- Article
- ISSN
- 1542-0752
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✦ Synopsis
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. Birth Defects Research (Part A), 2004. Published 2004 Wiley‐Liss, Inc.