Causes and consequences of maternal age-related aneuploidy in oocytes: a review

Although a positive correlation between aneuploidy and maternal age was first reported almost a century ago, the underlying mechanisms remain mostly unknown. Different hypotheses regarding age-related aneuploidy rise have been presented, but so far none of them can explain its full mechanism. Age-related aneuploidy is more likely to result from complex events taking place during the entire period of germ cell development, than from the failure of one particular mechanism. Recent findings confirm that the spindle assembly checkpoint (SAC) does not control and correct kinetochore-microtubule attachments in oocytes, enabling further propagation of aneuploidy, which has occurred in the earlier phases of oogenesis. In this review we will discuss the following hypotheses: the "limited oocyte pool" hypothesis, the "two hits" hypothesis, weakened centromeric cohesion and cohesin loss, different functions of the spindle assembly checkpoint and finally, changes in global gene expression.