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Updated: Oct 26, 2025
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
GAS6 ameliorates advanced age-associated meiotic defects in mouse oocytes by modulating mitochondrial function
Kyeoung-Hwa Kim1, Eun-Young Kim1, Kyung-Ah Lee1
1Department of Biomedical Science, Institute of Reproductive Medicine, College of Life Science, CHA University, Seongnam-si, Gyeonggi-do 13488, Korea.
Abstract:
Previously, we reported that the silencing of growth arrest-specific gene 6 (Gas6) expression in oocytes impairs cytoplasmic maturation by suppressing mitophagy and inducing mitochondrial dysfunction, resulting in fertilization failure. Here, we show that oocyte aging is accompanied by an increase in meiotic defects associated with chromosome misalignment and abnormal spindle organization. Intriguingly, decreased Gas6 mRNA and protein expression were observed in aged oocytes from older females. We further explored the effect of GAS6 on the quality and fertility of aged mouse oocytes using a GAS6 rescue analysis. After treatment with the GAS6 protein, aged oocytes matured normally to the meiosis II (MII) stage. Additionally, maternal age-related meiotic defects were reduced by GAS6 protein microinjection. Restoring GAS6 ameliorated the mitochondrial dysfunction induced by maternal aging. Ultimately, GAS6-rescued MII oocytes exhibited increased ATP levels, reduced ROS levels and elevated glutathione (GSH) levels, collectively indicating improved mitochondrial function in aged oocytes. Thus, the age-associated decrease in oocyte quality was prevented by restoring GAS6. Importantly, GAS6 protein microinjection in aged oocytes also rescued fertility. We conclude that GAS6 improves mitochondrial function to achieve sufficient cytoplasmic maturation and attenuates maternal age-related meiotic errors, thereby efficiently safeguarding oocyte quality and fertility.
Insights
Growth arrest-specific gene 6 (Gas6) is crucial for oocyte quality. Restoring Gas6 in aged oocytes improves mitochondrial function and reduces meiotic errors, thereby safeguarding fertility.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Gerontology
Background:
- Oocyte aging is linked to increased meiotic defects, including chromosome misalignment and abnormal spindle organization.
- Aging oocytes exhibit decreased expression of growth arrest-specific gene 6 (Gas6), a protein previously shown to be vital for cytoplasmic maturation and mitochondrial function.
Purpose of the Study:
- To investigate the role of Gas6 in maternal age-related oocyte aging and meiotic errors.
- To determine if restoring Gas6 levels can rescue the quality and fertility of aged oocytes.
Main Methods:
- Analysis of Gas6 expression in aged mouse oocytes.
- GAS6 protein rescue experiments involving microinjection into aged oocytes.
- Assessment of oocyte maturation, meiotic progression, mitochondrial function (ATP, ROS, GSH levels), and fertility.
Main Results:
- Aged oocytes from older females showed reduced Gas6 mRNA and protein levels.
- GAS6 protein microinjection in aged oocytes restored normal meiosis II (MII) stage maturation and reduced meiotic defects.
- Restoration of Gas6 ameliorated mitochondrial dysfunction, evidenced by increased ATP and glutathione, and reduced reactive oxygen species (ROS).
- GAS6-rescued oocytes demonstrated improved mitochondrial function and rescued fertility.
Conclusions:
- The age-associated decline in oocyte quality is partly due to decreased Gas6 expression.
- Restoring Gas6 levels in aged oocytes can prevent age-related decreases in quality and fertility by improving mitochondrial function and attenuating meiotic errors.
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