Faulty spindle checkpoint and cohesion protein activities predispose oocytes to premature chromosome separation and aneuploidy.

Aneuploidy accounts for a major proportion of human reproductive failures, mental and physical anomalies, and neoplasms. To heighten our understanding of normal and abnormal chromosome segregation, additional information is needed about the underlying molecular mechanisms of chromosome segregation. Although many hypotheses have been proposed for the etiology of human aneuploidy, there has not been general acceptance of any specific hypothesis. Moreover, it is important to recognize that many potential mechanisms exist whereby chromosome missegregation may occur. One area for investigating aneuploidy centers on the biochemical changes that take place during oocyte maturation. In this regard, recent results have shown that faulty mRNA of spindle-assembly checkpoint proteins and chromosome cohesion proteins may lead to aneuploidy. Also, postovulatory and in vitro aging of mouse oocytes has been shown to lead to decreased levels of Mad2 transcripts and elevated frequencies of premature centromere separation. The intent of this review is to highlight the major events surrounding chromosome segregation and to present the published results that support the premise that faulty chromosome cohesion proteins and spindle checkpoint proteins compromise accurate chromosome segregation.