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Updated: Jun 18, 2025
Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by
Li-Hua Fan1,2,3,4, Shu-Tao Qi2,5, Zhen-Bo Wang2,4
1Fertility Preservation Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
Abstract:
Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.
Insights
MEIKIN protein levels must be tightly regulated during oocyte maturation. Proper MEIKIN degradation and C-terminal phosphorylation by PLK1 are crucial for accurate chromosome segregation and preventing meiotic abnormalities.
Area of Science:
- Reproductive Biology
- Cell Biology
- Molecular Genetics
Background:
- Oocyte maturation failure and chromosome abnormalities contribute to infertility and developmental diseases.
- Accurate chromosome segregation during meiosis I relies on sister chromatid mono-orientation.
- MEIKIN is a germ cell-specific protein involved in regulating mono-orientation and centromeric cohesin protection during meiosis I.
Purpose of the Study:
- To investigate the role of MEIKIN expression dynamics and post-translational modification in mouse oocyte meiosis.
- To elucidate the mechanism and consequences of MEIKIN degradation during oocyte maturation.
- To determine the functional significance of MEIKIN phosphorylation by PLK1.
Main Methods:
- Analysis of MEIKIN expression and localization in mouse oocytes at different meiotic stages.
- Investigation of MEIKIN phosphorylation using in vitro and in vivo approaches.
- Exogenous expression of MEIKIN to study the effects of suppressed degradation on meiotic progression and chromosome segregation.
- Assessment of spindle assembly checkpoint (SAC) activity and cell cycle progression.
Main Results:
- MEIKIN is a maternal protein highly expressed before metaphase I (MI), degraded by metaphase II (MII) stage, and phosphorylated after germinal vesicle breakdown (GVBD).
- PLK1 mediates MEIKIN phosphorylation at its C-terminus, which is critical for its function.
- Suppression of MEIKIN degradation leads to chromosome misalignment, failure of cyclin B1 and securin degradation, and metaphase I arrest via a SAC-independent pathway.
- Overexpression of MEIKIN inhibits MII exit and early embryo development.
Conclusions:
- Proper regulation of MEIKIN levels through degradation and C-terminal phosphorylation by PLK1 is essential for the metaphase-anaphase transition in oocytes.
- Dysregulation of MEIKIN impacts chromosome segregation fidelity and meiotic progression.
- These findings provide insights into preventing meiotic abnormalities and understanding infertility causes.
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