DZ disturbed the spatio-temporal distribution of mitochondria during oocyte maturation, possibly by binding to peripheral-type benzodiazepine receptors on mitochondria, thus affecting the availability of ATP and calcium homeostasis. Precocious chiasma resolution and equational segregation of chromatids from functional univalents in first anaphase (predivision) may be responsible for this condition, a mechanism also discussed in the aetiology of maternal age-related aneuploidy. Some DZ-treated oocytes progressing to meiosis II exhibited one or multiple single chromatids. A significant fraction of meiotically delayed, metaphase I-blocked oocytes exposed to 25 microg/ml DZ contained univalents. Concomitantly, DZ induced spindle aberrations and displacement of chromosomes from the equator, but unlike in mitosis and in male meiosis most oocytes still possessed bipolar spindles. Hyperploidy was slightly increased in oocytes matured in the presence of 5 microg/ml DZ and became significantly elevated in oocytes matured with 25 microg/ml DZ, relative to controls. A concentration of 25 microg/ml DZ induced a pronounced delay in maturation and blocked a high percentage of oocytes in meiosis I. Spindle formation and cell cycle progression, the behaviour of chromosomes and the distribution of mitochondria were characterized with respect to induction of numerical chromosomal aberrations. In order to assess its aneugenic potential in mammalian oogenesis we exposed in vitro maturing mouse oocytes to the drug. The tranquilizer and anti-convulsant diazepam (DZ) is a suspected aneugen.
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