FSP1 regulates ferroptosis and mitochondrial function during mouse oocyte maturation

Area of Science:

• Reproductive Biology
• Cellular Biology
• Biochemistry

Background:

• Oocyte quality is vital for successful fertilization and embryonic development.
• Emerging evidence suggests ferroptosis, a regulated cell death, negatively impacts oocyte quality.
• The role of Ferroptosis suppressor protein 1 (FSP1) in oocyte meiotic maturation remains largely uncharacterized.

Purpose of the Study:

• To investigate the function of FSP1 in regulating mouse oocyte meiotic maturation.
• To determine the mechanistic link between FSP1, ferroptosis, and oocyte quality.
• To assess the impact of FSP1 inhibition on oocyte development and meiotic progression.

Main Methods:

• Analysis of FSP1 expression during oocyte meiotic maturation in mice.
• Pharmacological inhibition of FSP1 in oocytes.
• Assessment of meiotic progression, spindle integrity, and chromosome alignment.
• Measurement of intracellular iron levels, reactive oxygen species, and lipid peroxidation.
• Evaluation of ferroptosis-associated gene expression and mitochondrial function.

Main Results:

• FSP1 expression was detected in mouse oocytes throughout meiotic maturation and decreased in aged mice.
• FSP1 inhibition disrupted meiotic progression, causing spindle defects, chromosome misalignment, and meiotic arrest.
• Inhibition of FSP1 induced ferroptosis, evidenced by increased intracellular iron, reactive oxygen species, lipid peroxidation, and altered gene expression.
• Mitochondrial dysfunction, including aberrant distribution and impaired ATP production, was observed upon FSP1 inhibition.

Conclusions:

• FSP1 is a key regulator of oocyte meiotic maturation, essential for maintaining iron homeostasis and mitochondrial function.
• FSP1 inhibition triggers ferroptosis, leading to oocyte meiotic failure and compromised quality.
• These findings highlight FSP1 as a potential therapeutic target for improving oocyte quality in reproductive medicine.