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Aneuploidy induction in mouse spermatocytes
1GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Säugetiergenetik, Neuherberg, FRG.
Abstract:
Assays for aneuploidy are being developed within a coordinated research program sponsored by the Commission of the European Communities. The 10 known and suspect spindle poisons colchicine (COL), econazole (EZ), chloral hydrate (CH), hydroquinone (HQ), diazepam (DZ), thiabendazole (TB), cadmium chloride (CD), pyrimethamine (PY), thimerosal (TM) and vinblastine (VBL) were tested for aneuploidy induction in male germ cells. Two different criteria were used for the evaluation of slides from testicular material of (102/El x C3H/El)F1 mice at different times (6, 14 and 22 h) after treatment with different doses of each of the test chemicals. Secondary spermatocytes of mice were evaluated by chromosome counting to determine the induction of hyperploidy. The proportions of spermatogonial mitoses, first and second meiotic metaphases were determined in order to recognize an effect of the test chemicals on testicular cell proliferation. COL, EZ, CH, HQ and VBL clearly increased the frequencies of hyperploid secondary spermatocytes which indicated non-disjunction induction during the first meiotic division. DZ and CD were less effective but significantly positive (P less than 0.05). Concomitantly, COL, EZ, CH, HQ, DZ, CD and VBL induced meiotic delay in primary and/or secondary spermatocytes. It is concluded that meiotic delay may be indicative for aneuploidy induction and the evaluation of changes in testicular cell proliferation described here could serve as a prescreen and partially substitute the time-consuming counting of metaphase chromosomes in secondary spermatocytes.
Insights
Ten spindle poisons were tested for aneuploidy induction in male germ cells. Several chemicals, including colchicine (COL) and vinblastine (VBL), induced hyperploidy and meiotic delay, suggesting potential for prescreening.
Area of Science:
- Toxicology
- Genetics
- Reproductive Biology
Background:
- Aneuploidy, an abnormal chromosome number, is a significant concern in reproductive health.
- Developing reliable assays for aneuploidy induction is crucial for risk assessment.
- Spindle poisons are chemicals known to interfere with cell division.
Purpose of the Study:
- To evaluate the aneuploidy-inducing potential of 10 known and suspect spindle poisons in male germ cells.
- To assess the correlation between meiotic delay and aneuploidy induction.
- To establish a prescreening method for aneuploidy induction.
Main Methods:
- Testing of 10 spindle poisons (colchicine, econazole, chloral hydrate, hydroquinone, diazepam, thiabendazole, cadmium chloride, pyrimethamine, thimerosal, vinblastine) in (102/El x C3H/El)F1 mice.
- Evaluation of testicular material at 6, 14, and 22 hours post-treatment with varying doses.
- Chromosome counting in secondary spermatocytes for hyperploidy and assessment of spermatogonial mitoses and meiotic metaphases for cell proliferation effects.
Main Results:
- Colchicine (COL), econazole (EZ), chloral hydrate (CH), hydroquinone (HQ), and vinblastine (VBL) significantly increased hyperploid secondary spermatocytes, indicating non-disjunction.
- Diazepam (DZ) and cadmium chloride (CD) showed significant (P < 0.05) but less pronounced aneuploidy induction.
- COL, EZ, CH, HQ, DZ, CD, and VBL induced meiotic delay in primary and/or secondary spermatocytes.
Conclusions:
- Meiotic delay can serve as an indicator for aneuploidy induction.
- Assessing changes in testicular cell proliferation offers a valuable prescreening method for aneuploidy.
- This approach can partially replace time-consuming chromosome counting in secondary spermatocytes.