Meiotic Origins of Maternal Age-Related Aneuploidy

Chromosome segregation errors in female meiosis lead to aneuploidy in the resulting egg and embryo, making them one of the leading genetic causes of spontaneous abortions and developmental disabilities in humans. It is known that aneuploidy of meiotic origin increases dramatically as women age, and current evidence suggests that most errors occur in meiosis I. Several hypotheses regarding the cause of maternal age-related aneuploidy have been proposed, including recombination errors in early meiosis, a defective spindle assembly checkpoint in meiosis I, and deterioration of sister chromatid cohesion with age. This review discusses findings in each area, and focuses especially on recent studies suggesting that deterioration of cohesion with increasing maternal age is a leading cause of age-related aneuploidy.