Disorganization, Meiotic Spindle leads to Altered, Meiotic chromosome dynamics

Incorrect spindle organization refers to lack of the bipolar organization of the spindle within the cell. This bipolar organization is required to assure that chromosomes will align correctly to the metaphase plate prior to equal division between the daughter cells. Alternatively, incorrect spindle formation can lead to shorter spindle fibers and/or incorrect length of these fibers, which leads to chromosome misalignment.

In this KER, chemicals that cause spindle disorganization lead to altered meiotic chromosome dynamics. The relationship between spindle disorganization and altered chromosome dynamics can occur in both somatic and in germ cells; however, this relationship focuses on female meiotic chromosomes because of the differences in how the meiotic spindle is assembled in oocytes with respect to other cell types (i.e., lack of centrioles and dependency on microtubule organizing centers). Interestingly, some studies investigating the effects of protein deficiencies in mouse oocytes provide direct evidence of the events involved in the KER [McGuinnes et al., 2009; Ou et al., 2010; Baumann et al., 2017]. For example, targeting deletion of Bub1 in mouse oocytes caused dysregulation of spindle assembly and leads to defective chromosome congression [McGuinness et al., 2009]. After depletion of p38a in mouse oocytes, a MTCO component, aberrant spindle organization, including defective or multipolar spindles are more than 3 times more frequent than in control mice, while there is an 8-fold increase in chromosome congression defects [Ou et al., 2010]. Finally, in a study carried out using an oocyte conditional pericentrin knockout mouse model and live cell imaging, alterations in spindle size have been observed, together with delay in meiotic spindle formation following in vitro culture of cumulus-enclosed oocytes. These abnormalities were associated with a significant increase in the number of unattached kinetochores and merotelic attachments, as well as, an increase in misaligned and uncongressed chromosomes [Baumann et al., 2017].

Due to the lack of solid evidence about the response-response relationship modulating factors cannot be identified in this KER.

Although there are no inconsistent results reported, it is important to note that very few studies have measured chromosome dynamics in oocytes in general. Thus, there is a large amount of uncertainty surrounding the qualitative and quantitative association between these two endpoints.

Although this KER has only been measured in mouse oocytes, the process of meiosis, spindle formation and chromosome congression in eggs is thought to be similar across mammalian species.