How oocytes try to get it right: spindle checkpoint control in meiosis

Abstract

The generation of a viable, diploid organism depends on the formation of haploid gametes, oocytes, and spermatocytes, with the correct number of chromosomes. Halving the genome requires the execution of two consecutive specialized cell divisions named meiosis I and II. Unfortunately, and in contrast to male meiosis, chromosome segregation in oocytes is error prone, with human oocytes being extraordinarily "meiotically challenged". Aneuploid oocytes, that are with the wrong number of chromosomes, give rise to aneuploid embryos when fertilized. In humans, most aneuploidies are lethal and result in spontaneous abortions. However, some trisomies survive to birth or even adulthood, such as the well-known trisomy 21, which gives rise to Down syndrome (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012). A staggering 20-25 % of oocytes ready to be fertilized are aneuploid in humans. If this were not bad enough, there is an additional increase in meiotic missegregations as women get closer to menopause. A woman above 40 has a risk of more than 30 % of getting pregnant with a trisomic child. Worse still, in industrialized western societies, child birth is delayed, with women getting their first child later in life than ever. This trend has led to an increase of trisomic pregnancies by 70 % in the last 30 years (Nagaoka et al. in Nat Rev Genet 13:493-504, 2012; Schmidt et al. in Hum Reprod Update 18:29-43, 2012). To understand why errors occur so frequently during the meiotic divisions in oocytes, we review here the molecular mechanisms at works to control chromosome segregation during meiosis. An important mitotic control mechanism, namely the spindle assembly checkpoint or SAC, has been adapted to the special requirements of the meiotic divisions, and this review will focus on our current knowledge of SAC control in mammalian oocytes. Knowledge on how chromosome segregation is controlled in mammalian oocytes may help to identify risk factors important for questions related to human reproductive health.

True Nondisjunction of Whole Bivalents in Oocytes with Attachment and Congression Defects

“…Despite the fact that we can explain the increase of aneuploidy coincidently with maternal age by deterioration of cohesion between sister chromatids [Chiang et al, 2010;Lister et al, 2010] due to the absence of turnover of the cohesin complex during a prolonged prophase arrest [Revenkova et al, 2010;Tachibana-Konwalski et al, 2010], we are still uncertain why the aneuploidy is so high even in oocytes from young individuals in comparison to meiosis in yeast and Drosophila [Hassold and Hunt, 2001]. One of the mechanism, which likely contributes to this higher aneuploidy rate, is the spindle assembly checkpoint (SAC) and specifically changes to its function in oocytes compared to somatic cells [Mailhes, 2008;Jones and Lane, 2013;Touati and Wassmann, 2015;Collins and Jones, 2016].In a previous study, we demonstrated that the SAC in oocytes is unable to detect extensive chromosome alignment and congression defects by using animals generated by crossbreeding of 2 different mouse species, Mus mus- …”

The resolution of ambiguity as the basis for life: A cellular bridge between Western reductionism and Eastern holism

“…These proximate markers of environmental stress must be purposed towards the long-term preservation of homeostatic status according to the ultimate primordial rules embodied within the First Principles of Physiology. The cytoskeleton can therefore be considered a governing aspect of homeostasis in addition to mitotic and meiotic division (Prosser and Pelletier, 2017; Touati and Wasserman, 2016), quite in opposition to convention. For example, when yeast, a simple unicellular eukaryote, is put into microgravity, it loses its ability to polarize and bud (Purevdorj-Gage, Sheehan and Hyman, 2006).…”

Cell Cycle Regulators in Female Meiosis of Drosophila melanogaster

“…A role for the SAC in meiosis has been most clearly established in the mouse where it is important for delaying anaphase I under normal conditions and under conditions in which the spindle is disrupted [50]. A role for the SAC in Drosophila is suggested by the protein localization and mutant phenotype for the essential SAC component, Mps1 (also known as Ald) [51].…”