GAS6 ameliorates advanced age-associated meiotic defects in mouse oocytes by modulating mitochondrial function

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.