Altered, Meiotic chromosome dynamics leads to Altered, Chromosome number

Although there are no inconsistent results reported, it is important to note that very few studies have measured chromosome dynamics and induction of aneuploidy in oocytes.

Data are available on the dose-response relationship for aneuploidy induction in oocytes (KEdownstream) treated with colchicine [Mailhes et al., 1988; Mailhes et al., 1990], vinblastine [Russo and Pacchierotti, 1988; Mailhes et al., 1993] or 2-methoxyestradiol [Eichenlaub-Ritter et al., 2007], which are consistent with the threshold relationship established in mitotic cells [Elhajouji et al., 2011]. Unfortunately, dose-effect relationships have not been established for chromosome dynamics alterations (KEupstream) at the first meiotic division. Thus, it is not possible to establish the shape of the response-response relationship between chromosome dynamics alteratiions (KEupstream) and altered chromosome nubmer in oocytes (KEdownstream).

As noted before, chromosome dynamics on the metaphase plate of oocytes may last a few hours before anaphase onset. The first meiotic anaphase lasts about 25 min equally distributed between anaphase-1, characterized by increased spindle length and movement of chromosomes towards the poles, and anaphase-2 at the end of which chromosomes reach the poles and aggregate into condensed clusters [Wei et al., 2018]. Thus, it is expected that alterations of chromosome number in the oocyte (KEdownstream) would lag alterations of meiotic chromosome dynamics (KEupstream) by hours, although no studies have been carried out until now to specifically address the time-scale of events linking chromosome dynamics alteratiions (KEupstream) and altered chromosome nubmer in oocytes (KEdownstream).

In mitotic and meiotic cells, anaphase onset and ensuing chromosome distribution is under checkpoint control that may delay anaphase onset until chromosomes are correctly aligned on the spindle equator, as signaled by specific molecular events [Nagaoka et al., 2012; Musacchio et al., 2015; Webster and Schuh, 2017]. Although the SAC in mammalian oocytes is deemed to be more tolerant to the presence of unaligned chromosomes, its role in preventing aneuploidy is proven in genetically modified or silenced systems [Mailhes and Marchetti 2010]. These checkpoint and signaling mechanisms therefore are expected to act as feedback loops, which may influence the time-scale of the KER between KEupstream (altered chromosome dynamics) and altered chromosome number in the oocyte (KEdownstream).