Biochemical and cytogenetic changes in postovulatory and in vitro aged mammalian oocytes: a predisposition to aneuploidy

Aneuploidy represents the most prevalent genetic disorder of man. Its association with spontaneous abortions, mental and physical retardation, and numerous malignant cells is well-known. Unfortunately, little is known about the causes and even less about the underlying molecular mechanisms of aneuploidy, especially in mammalian germ cells. Although several etiologies have been proposed for describing human aneuploidy, the only consistent finding remains its positive correlation with maternal age. At the outset, it is essential to point out that there exist numerous potential causes and mechanisms for the etiology of aneuploidy. Nevertheless, information about the molecular mechanisms of chromosome segregation in various species is providing a foundation for research designed to investigate the causes and mechanisms of aneuploidy. The intent of this review is to propose that the biochemical reactions and cellular organelles responsible for accurate chromosome segregation become compromised during postovulatory and in vitro oocyte aging; thus, increasing the probability of faulty chromosome segregation. Recent data have shown that the efficacies of the spindle assembly checkpoint and the chromosome cohesion proteins diminish as oocytes age postovulation and during in vitro culture. Such changes represent potential models for studying aneuploidy. Prior to describing the biochemical and cellular organelle changes found in aged oocytes and their effect on chromosome segregation, an overview of the molecular details surrounding chromosome segregation is presented.