RT Journal Article
SR Electronic
T1 Initial spindle formation at the oocyte center protects against incorrect kinetochore-microtubule attachment and aneuploidy in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.28.176594
DO 10.1101/2020.06.28.176594
A1 Jessica N. Kincade
A1 Ahmed Z. Balboula
YR 2020
UL http://biorxiv.org/content/early/2020/06/28/2020.06.28.176594.abstract
AB Aneuploidy is the leading genetic cause of miscarriage and infertility in women and occurs frequently in oocytes. Spindle formation and positioning are two critical events that must be regulated tightly to avoid erroneous chromosome segregation. Following nuclear envelope breakdown (NEBD), the spindle is assembled centrally before migrating towards the cortex to allow the first asymmetric division. The biological significance of the primary central positioning of the spindle is unknown. Because the spindle forms where NEBD occurs, whether positioned at the center or at the cortex of the cell, full-grown GV (prophase I) oocytes were collected from CF-1 mice (6-8 weeks old) and sorted according to the position of the GV into three groups: central, intermediate, and peripheral. Approximately 50% of the cells exhibited a central GV position, while 25% of cells showed a peripheral GV position. These proportions were similar to those obtained by histological evaluation of ovarian oocytes in 6-8 week mice, but not to those of mice aged less than 5 weeks, which tended to have a majority of peripherally positioned GVs. When peripheral GV oocytes were matured in vitro, GVs (88%) migrated towards the center and NEBD (and spindle assembly) occurred either at the center of the cell or during migration. The percentages of NEBD and polar body (PB) extrusion did not vary significantly among groups. Importantly, peripheral GV oocytes had a significant increase of abnormal K-MT attachments at metaphase I (Met I) and showed a significant increase of aneuploidy at metaphase II (Met II) when compared to central GV oocytes. Interestingly, peripheral GV oocytes that were able to achieve full GV relocation to the center were half as likely to experience aneuploidy when compared to peripheral GV oocytes unable to achieve relocation. These results indicate that preferential central spindle formation is an insurance mechanism to protect against incorrect K-MT attachments and aneuploidy.Competing Interest StatementThe authors have declared no competing interest.