Differential chromosome behaviour in mammalian oocytes exposed to the tranquilizer diazepam in vitro

There are several reports demonstrating that aneugens may preferentially af fect segregation of particular chromosomes in somatic cells. Much less is k nown on specific susceptibility of individual chromosomes to non-disjunctio n in mammalian meiosis in response to chemical exposures. To explore possib le chromosome-specific behaviour and susceptibility to errors in chromosome segregation in mammalian oogenesis we employed spindle immunofluoresecence in combination with FISH with chromosome-specific probes to analyse congre ssion of chromosomes X, 8 and 16 in diazepam (DZ)-treated, meiotically dela yed meiosis I oocytes of the mouse. Concomitantly, we assessed the suscepti bility of homologues to precociously segregate prior to anaphase I during D Z-induced meiotic arrest. About 50% of all oocytes exposed to 25 mug/ml DZ became meiotically delayed. Chromosomes failed to congress at the spindle e quator in one-third of these meiosis I oocytes. The X chromosome was signif icantly more often located away from the spindle equator as compared with t he expected random behaviour. Concomitantly, DZ exposure induced untimely s egregation of homologous chromosomes of the gonosome and the autosomes in m eiosis I. This occurred with similar frequencies. The observations confirm that DZ perturbs cell cycle progression, interferes with chromosome alignme nt, causes predivision and thus may predispose mammalian oocytes to errors in chromosome segregation. For the first time, chromosome-specific behaviou r is reported in female meiosis in response to exposure to an aneugenic che mical.