Spindle Assembly Checkpoint in oocytes and zygotes and its importance for human aneuploidy

The surveillance mechanism called Spindle Assembly Checkpoint (SAC) monitors the status of the division spindle and prevents anaphase entry in the presence of anomalies that could result in erroneous segregation of the chromosomes. Disturbances in SAC activity during female meiosis promotes formation of aneuploid oocytes and results in associated reproductive disorders like pregnancy loss or birth defects. In a similar way embryonic aneuploidy and pregnancy loss may occur due to SAC deficiency in the zygotes and early embryos. The production of aneuploid oocytes rises drastically in females with advancing age due to failure in chromosome cohesion in oocytes from old mice. Whether the decreased SAC efficiency contributes to maternal age-related aneuploidy remains disputable. Oocytes from LT/Sv mice are unable to timely switch off the SAC activity [1]. As a result the majority of LT/Sv oocytes block at the metaphase of the first meiosis instead to progress to the second meiotic cycle. The defect in the ceasing SAC activity occurs also in LT/Sv zygotes as evidenced by enormously prolonged duration of the metaphase in these cells [2]. Thus, LT/Sv mice represent an valuable model to study the SAC function in the oocytes and at the earliest stages of development. Importantly, the proportion of LT/Sv oocytes which arrest at the first meiosis drops significantly in the older females [3], thus providing the model to study the relationship between SAC activity and maternal-age related aneuploidy.