Mechanisms and risk of chemically induced aneuploidy in mammalian germ cells

Francesca Pacchierotti, Roberto Ranaldi

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Aneuploidy is a pathological condition that affects 35% of human spontaneous abortions and 0.3% of livebirths. In spite of the increasing knowledge about molecular mechanisms of meiosis and chromosome segregation, maternal age remains the only ascertained aetiological factor. Genetically modified mouse models have been produced that show increased incidence of aneuploid gametes or abnormalities in meiotic recombination and synapsis. They suggest that genetic polymorphisms might also be involved in the aetiology of human germ cell aneuploidy. Experimental studies in the mouse have identified chemicals that can induce aneuploidy in male and female germ cells. Compounds affecting spindle assembly/dynamics are potent aneugens for oocytes and less so also for spermatocytes. They are active at acute doses during a short time interval preceding the metaphase-to-anaphase transition. Topoisomerase inhibitors are also meiotic aneugens which act on the recombination process; for the first time, the production of viable aneuploid mouse progeny was shown after paternal treatment with etoposide. A comparison between in vitro and in vivo effects of suspect aneugens demonstrates that there are biological mechanisms protecting mammalian oocytes from acute exposures to exogenous chemicals. Endocrine disruptors are a novel group of compounds that might affect chromosome segregation at meiosis. Data on bisphenol-A suggest that such chemicals could be active at low chronic exposure levels, but this hypothesis needs to be confirmed by further experiments. Experiments on cultured mouse oocytes treated with inhibitors of biochemical reactions involved in the regulation of chromosome segregation point to possible new mechanisms of action of environmental aneugenus. © 2006 Bentham Science Publishers Ltd.
Original languageEnglish
Pages (from-to)1489 - 1504
Number of pages16
JournalCurrent Pharmaceutical Design
Volume12
Issue number12
DOIs
Publication statusPublished - Apr 2006
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

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