Transient exposure to the Eg5 kinesin inhibitor monastrol leads to syntelic orientation of chromosomes and aneuploidy in mouse oocytes

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2004-04, Vol.559 (1-2), p.153-167
• Main Authors: Mailhes, John B, Mastromatteo, Colette, Fuseler, John W
• Format: Article
• Language: English
• Subjects: Aneuploidy; Biological and medical sciences; Chromosome; Chromosome aberrations; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Medical genetics; Medical sciences; Monastrol; Oocyte; Toxicology
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2004.01.001

Aneuploidy may result from abnormalities in the biochemical pathways and cellular organelles associated with chromosome segregation. Monastrol is a reversible, cell-permeable, non-tubulin interacting inhibitor of the mitotic kinesin Eg5 motor protein which is required for assembling and maintaining the mitotic spindle. Monastrol can also impair centrosome separation and induce monoastral spindles in mammalian somatic cells. The ability of monastrol to alter kinesin Eg5 and centrosome activities and spindle geometry may lead to abnormal chromosome segregation. Mouse oocytes were exposed to 0 (control), 15, 30, and 45μg/ml monastrol in vitro for 6h during meiosis I and subsequently cultured for 17h in monastrol-free media prior to cytogenetic analysis of metaphase II oocytes. A subset of oocytes was cultured for 5h prior to processing cells for meiotic I spindle analysis. Monastrol retarded oocyte maturation by significantly (P