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Chemically induced aneuploidy in female germ cells
1ICI Pharmaceuticals Div., Alderley Park, Macclesfield, Cheshire, UK.
Mutagenesis
|May 1, 1988
Summary
Mice treated with spindle poisons colchicine and colcemid, or ICI 109,081, produced embryos with chromosome abnormalities. Colchicine induced polyploidy, while colcemid and ICI 109,081 caused polyploidy and aneuploidy, depending on dosing time.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Toxicology
Background:
- Oocyte maturation is a critical process for successful fertilization and embryonic development.
- Spindle poisons and maturation inhibitors can disrupt chromosome segregation during meiosis.
Purpose of the Study:
- To investigate the effects of specific chemical agents on chromosome integrity in early mouse embryos.
- To determine the impact of timing of exposure to these agents on the types and frequencies of chromosomal aberrations.
Main Methods:
- Female mice were synchronized for ovulation and administered colcemid, colchicine, ICI 109,081, or saline.
- Dosed females were mated, and resulting first-cleavage embryos were analyzed for numerical chromosome aberrations.
- Exposure timing relative to ovulation (3h or 12h prior) was varied.
Main Results:
- Colchicine treatment resulted in polyploid embryos, with 100% observed when dosed 12h prior to ovulation.
- Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos.
- Colcemid-induced aberrations were primarily seen at 3h prior to ovulation (4% polyploid, 24% aneuploid), while ICI 109,081 effects were more pronounced at 12h prior (10% polyploid, 3% aneuploid).
Conclusions:
- Colchicine, colcemid, and ICI 109,081 can induce numerical chromosome aberrations in mouse embryos.
- The timing of exposure to these agents significantly influences the type and incidence of observed abnormalities.
- These findings highlight the sensitivity of oocytes to spindle-disrupting agents during maturation and fertilization.