scholarly journals Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes

Development ◽  
2012 ◽  
Vol 139 (11) ◽  
pp. 1941-1946 ◽  
Author(s):  
L. Gui ◽  
H. Homer
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Chromosomal Position ◽  
Mouse Oocytes

scholarly journals DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Josie K. Collins ◽  
Simon I. R. Lane ◽  
Julie A. Merriman ◽  
Keith T. Jones
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Meiotic Arrest ◽  
Mouse Oocytes

scholarly journals APCFZR1 prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing

2012 ◽  
Vol 23 (20) ◽  
pp. 3970-3981 ◽  
Author(s):  
Janet E. Holt ◽  
Simon I. R. Lane ◽  
Phoebe Jennings ◽  
Irene García-Higuera ◽  
Sergio Moreno ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Cell ◽  
Meiotic Spindle ◽  
Genome Integrity ◽  
Mitotic Cell Cycle ◽  
Anaphase Promoting Complex ◽  
Mouse Oocytes ◽  
M Phase ◽  
Chromosome Nondisjunction

FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to the G2/M transition. Here we report that mouse oocytes lacking FZR1 undergo passage through meiosis I that is accelerated by ∼1 h, and this is due to an earlier onset of spindle assembly checkpoint (SAC) satisfaction and APCCDC20 activity. However, loss of FZR1 did not compromise SAC functionality; instead, earlier SAC satisfaction was achieved because the bipolar meiotic spindle was assembled more quickly in the absence of FZR1. This novel regulation of spindle assembly by FZR1 led to premature bivalent attachment to microtubules and loss of kinetochore-bound MAD2. Bivalents, however, were observed to congress poorly, leading to nondisjunction rates of 25%. We conclude that in mouse oocytes FZR1 controls the timing of assembly of the bipolar spindle and in so doing the timing of SAC satisfaction and APCCDC20 activity. This study implicates FZR1 as a major regulator of prometaphase whose activity helps to prevent chromosome nondisjunction.

scholarly journals CDC6 regulates both G2/M transition and metaphase-to-anaphase transition during the first meiosis of mouse oocytes

2019 ◽  
Author(s):  
Zi-Yun Yi ◽  
Tie-Gang Meng ◽  
Xue-Shan Ma ◽  
Jian Li ◽  
Chun-Hui Zhang ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Time Lapse ◽  
Cyclin B1 ◽  
Meiotic Spindle ◽  
G2 Arrest ◽  
Mouse Oocytes ◽  
Summary Statement ◽  
Initiation Of Dna Replication ◽  
Oocyte Meiotic Maturation

AbstractCell division cycle protein CDC6 is essential for the initiation of DNA replication. CDC6 was recently shown to inhibit the microtubule-organizing activity of the centrosome. Here, we show that CDC6 is localized to the spindle from Pro-MI to MII stages of oocytes, and it plays important roles at two critical steps of oocyte meiotic maturation. CDC6 depletion facilitated the G2/M transition (GV breakdown, GVBD) through regulation of Cdh1 and cyclin B1 expression and CDK1 phosphorylation in a GVBD-inhibiting culture system containing milrinone. Furthermore, GVBD was significantly decreased after knockdown of cyclin B1 in CDC6-depleted oocytes, indicating that the effect of CDC6 loss on GVBD stimulation was mediated, at least in part, by raising cyclin B1. Knockdown of CDC6 also caused abnormal localization of γ-tubulin, resulting in defective spindles, misaligned chromosomes, cyclin B1 accumulation and spindle assembly checkpoint (SAC) activation, leading to significant Pro-MI/MI arrest and PB1 extrusion failure. These phenotypes were also confirmed by time-lapse live cell imaging analysis. The results indicate that CDC6 is indispensable for maintaining G2 arrest of meiosis and functions in G2/M checkpoint regulation in mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.Summary statementWe show that CDC6 is indispensable for maintaining G2 arrest of mouse oocytes. Moreover, CDC6 is also a key player regulating meiotic spindle assembly and metaphase-to-anaphase transition in meiotic oocytes.

scholarly journals Vitrification-induced activation of lysosomal cathepsin B perturbs spindle assembly checkpoint function in mouse oocytes

2020 ◽  
Vol 26 (9) ◽  
pp. 689-701
Author(s):  
Ahmed Z Balboula ◽  
Karen Schindler ◽  
Tomoya Kotani ◽  
Manabu Kawahara ◽  
Masashi Takahashi
Keyword(s):  
Cathepsin B ◽  
Spindle Assembly Checkpoint ◽  
Caspase 3 ◽  
Polar Body ◽  
Spindle Assembly ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Dependent Manner ◽  
Mouse Oocytes ◽  
First Polar Body

Abstract As the age of child-bearing increases and correlates with infertility, cryopreservation of female gametes is becoming common-place in ART. However, the developmental competence of vitrified oocytes has remained low. The underlying mechanisms responsible for reduced oocyte quality post-vitrification are largely unknown. Mouse cumulus–oocyte complexes were vitrified using a cryoloop technique and a mixture of dimethylsulphoxide, ethylene glycol and trehalose as cryoprotectants. Fresh and vitrified/thawed oocytes were compared for chromosome alignment, spindle morphology, kinetochore-microtubule attachments, spindle assembly checkpoint (SAC) and aneuploidy. Although the majority of vitrified oocytes extruded the first polar body (PB), they had a significant increase of chromosome misalignment, abnormal spindle formation and aneuploidy at metaphase II. In contrast to controls, vitrified oocytes extruded the first PB in the presence of nocodazole and etoposide, which should induce metaphase I arrest in a SAC-dependent manner. The fluorescence intensity of mitotic arrest deficient 2 (MAD2), an essential SAC protein, at kinetochores was reduced in vitrified oocytes, indicating that the SAC is weakened after vitrification/thawing. Furthermore, we found that vitrification-associated stress disrupted lysosomal function and stimulated cathepsin B activity, with a subsequent activation of caspase 3. MAD2 localization and SAC function in vitrified oocytes were restored upon treatment with a cathepsin B or a caspase 3 inhibitor. This study was conducted using mouse oocytes, therefore confirming these results in human oocytes is a prerequisite before applying these findings in IVF clinics. Here, we uncovered underlying molecular pathways that contribute to an understanding of how vitrification compromises oocyte quality. Regulating these pathways will be a step toward improving oocyte quality post vitrification and potentially increasing the efficiency of the vitrification program.

scholarly journals The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes

2004 ◽  
Vol 167 (6) ◽  
pp. 1037-1050 ◽  
Author(s):  
Chizuko Tsurumi ◽  
Steffen Hoffmann ◽  
Stephan Geley ◽  
Ralph Graeser ◽  
Zbigniew Polanski
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Dominant Negative ◽  
Meiotic Spindle ◽  
Anaphase Promoting Complex ◽  
Mouse Oocytes ◽  
Cytostatic Factor ◽  
C Complex ◽  
Meiosis I

In Xenopus oocytes, the spindle assembly checkpoint (SAC) kinase Bub1 is required for cytostatic factor (CSF)-induced metaphase arrest in meiosis II. To investigate whether matured mouse oocytes are kept in metaphase by a SAC-mediated inhibition of the anaphase-promoting complex/cyclosome (APC/C) complex, we injected a dominant-negative Bub1 mutant (Bub1dn) into mouse oocytes undergoing meiosis in vitro. Passage through meiosis I was accelerated, but even though the SAC was disrupted, injected oocytes still arrested at metaphase II. Bub1dn-injected oocytes released from CSF and treated with nocodazole to disrupt the second meiotic spindle proceeded into interphase, whereas noninjected control oocytes remained arrested at metaphase. Similar results were obtained using dominant-negative forms of Mad2 and BubR1, as well as checkpoint resistant dominant APC/C activating forms of Cdc20. Thus, SAC proteins are required for checkpoint functions in meiosis I and II, but, in contrast to frog eggs, the SAC is not required for establishing or maintaining the CSF arrest in mouse oocytes.

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