Induction of aneuploidy in male mouse germ cells detected by the sperm–FISH assay: a review of the present data base

Abstract

Multicolour fluorescence in situ hybridization (FISH) with chromosome-specific DNA-probes can be used to assess aneuploidy (disomy) and diploidy in sperm of any species provided the DNA-probes are available. In the present EU research project, DNA-probes for mouse chromosomes 8, X and Y were employed each labelled with different colours. Male mice were treated with the test chemicals and sperm were sampled from the C audae epididymes 22–24 days later to allow spermatocytes exposed during meiosis to develop into mature sperm. At present, the data base comprises 10 chemicals: acrylamide (AA), carbendazim (CB), colchicine (COL), diazepam (DZ), griseofulvin (GF), omeprazole (OM), taxol (TX), thiobendazole (TB), trichlorfon (TF) and vinblastine (VBL). Of these, COL and TF induced disomic sperm only. DZ and GF induced disomic and diploid sperm, while CB and TB induced diploid sperm only. VBL gave contradictory results in repeated experiments in an inter-laboratory comparison. AA, OM and TX did not induce an increase in disomic or diploid sperm at the doses used. The induction of aneuploidy by DZ was also tested in humans. Sperm samples from patients after attempted suicide and from patients with chronic Valium ® abuse were evaluated using human DNA-probes specific for chromosomes 1,16, 21, X and Y. A quantitative comparison between mouse and man indicates that male meiosis in humans is 10–100 times more sensitive than in mice to aneuploidy induction by DZ. The positive response of mice to TF supports the hypothesis by Czeizel et al. [Lancet 341 (1993) 539] that TF may be causally related to the occurrence of congenital abnormality clusters in a Hungarian village.