Title:
Intrinsic and age-related sources of aneuploidy in eggs
Tomoya Kitajima
Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology
Abstract:
Aneuploidy is a leading cause of pregnancy loss and birth defects. Most of the aneuploidy originates from chromosome segregation errors during meiosis I in oocytes. The frequency of the errors during meiosis I in oocytes is much higher than that of any other cell division and increases with age. In this seminar, we discuss intrinsic and age-related sources of chromosome segregation errors during meiosis I in oocytes. We show that in mouse oocytes from naturally aged mice, the majority of chromosome segregation errors are preceded by premature separation of bivalents (homologous chromosome pairs) into univalents (sister chromatid pairs). The univalents fail to maintain correct kinetochore-microtubule attachments because of a loss of tension between homologous kinetochores and a meiosis I-specific chromosome property that destabilizes correct microtubule attachments. This can activate the spindle assembly checkpoint, but it fails to arrest the oocyte because the checkpoint signalling is diluted by the large cytoplasm of oocytes. Moreover, the univalents can undesirably stabilize incorrect bipolar microtubule attachment of sister kinetochores, which silences the spindle checkpoint. Consequently, the oocyte undergoes chromosome segregation with kinetochore-microtubule attachment errors, frequently resulting in balanced and unbalanced predivision (premature segregation) of sister chromatids during meiosis I. Our study suggests that oocytes are prone to errors due to oocyte-intrinsic chromosomal and cytoplasmic properties and age-related loss of chromosome cohesion.
References:
1.Sakakibara, Y. et al. Bivalent separation into univalents precedes age-related meiosis I errors in oocytes. Nat Commun 6, 7550 (2015).
2.Yoshida, S. et al. Inherent instability of correct kinetochore-microtubule attachments during meiosis I in oocytes. Dev. Cell 33, 589–602 (2015).
