Gefitinib reduces oocyte quality by disturbing meiotic progression

Area of Science:

• Reproductive Toxicology
• Cell Biology
• Oncology

Background:

• Gefitinib is a first-line treatment for advanced non-small cell lung cancer (NSCLC).
• Known adverse effects include nausea, edema, appetite loss, and rash.
• The reproductive toxicity of gefitinib remains poorly understood.

Purpose of the Study:

• To investigate the effects of gefitinib on oocyte quality and maturation.
• To identify molecular mechanisms underlying gefitinib-induced reproductive toxicity.

Main Methods:

• Oocytes were cultured with varying concentrations of gefitinib (1, 2, 5, 10 μM).
• Assessed oocyte maturation rates (germinal vesicle breakdown, polar body extrusion).
• Analyzed molecular changes: CDK1 phosphorylation, cyclin B1 localization, spindle/chromosome assembly, mitochondria dynamics, apoptosis.

Main Results:

• 1 μM gefitinib had no effect on oocyte maturation.
• 5 μM gefitinib significantly inhibited meiotic progression (GVBD, PBE).
• Gefitinib disrupted spindle assembly, chromosome alignment, and mitochondria, inducing aneuploidy and apoptosis.

Conclusions:

• Gefitinib exhibits reproductive toxicity, particularly at higher concentrations.
• The drug interferes with critical oocyte maturation events and molecular pathways.
• Findings provide evidence for gefitinib's adverse effects on female fertility in cancer patients.