Pathogenesis of ethanol‐induced limb reduction defects in mice
- 1 October 1992
- journal article
- developmental pharmacology-and-toxicology
- Published by Wiley in Teratology
- Vol. 46 (4), 323-332
- https://doi.org/10.1002/tera.1420460403
Abstract
Acute administration of dosages of 2.5, 2.8, or 2.9 g/kg of ethanol to pregnant C57BL/6J mice on gestational day 9¼ resulted in major malformations of the forelimb including postaxial ectrodactyly, preaxial syndactyly, and reduction defects involving intermediate digits. The incidence and severity of these defects was positively correlated with dosage. Sidedness of the defects was also dose-dependent. In affected embryos, excessive amounts of cell death were notable within 5–9 hr of treatment initiation in selected cell populations. Cell death was primarily distributed in two regions of the developing limb bud—a ventrodistal ectodermal cell population (apical ectodermal ridge) and a proximal mesenchymal cell population. The patterns of cell death observed appear to be pathogenically related to the limb defects noted at later stages. In particular, it would appear that the deficiencies in the apical ectodermal ridge resulting from ethanol-induced cell death can account for virtually all the subsequent limb defects.Keywords
This publication has 26 references indexed in Scilit:
- Retinoic‐acid‐induced limb‐reduction defects: Perturbation of zones of programmed cell death as a pathogenetic mechanismTeratology, 1989
- Cell cycle alterations and cell death in cyclophosphamide teratogenesisTeratogenesis, Carcinogenesis, and Mutagenesis, 1989
- Major limb malformations following intrauterine exposure to ethanol: Two additional cases and literature reviewTeratology, 1986
- A biometrical genetic analysis of ethanol response in selectively bred Long-Sleep and Short-Sleep miceBehavior Genetics, 1984
- A critical review of the McCredie-McBride hypothesis of neural crest influence on limb morphogenesisTeratology, 1983
- Neural crest ablation and limb morphogenesisJournal of Experimental Zoology, 1983
- The classification and development of cadmium-induced limb defects in miceTeratology, 1982
- The early limb deformity caused by acetazolamideTeratology, 1979
- Relationship of temporal patterns of cell death and development to malformations in the rat limb. Possible mechanisms of teratogenesis with inhibitors of DNA synthesisTeratology, 1973
- Clostridium botulinumType F from Marine SedimentsScience, 1965