Pemetrexed negatively impacts embryonic development by inducing oxidative stress in mouse oocytes

Area of Science:

• Reproductive biology
• Toxicology
• Cancer drug research

Background:

• Chemotherapy patients often desire children, but the impact of specific drugs like pemetrexed on female fertility is not well understood.
• Pemetrexed is an antifolate chemotherapy agent used in cancer treatment, known for its apoptotic toxicity.

Purpose of the Study:

• To investigate the effects of pemetrexed exposure on female germ cells, specifically oocyte quality and fertility.
• To elucidate the underlying mechanisms by which pemetrexed may impair oocyte development and function.

Main Methods:

• Exposure of mouse oocytes to pemetrexed.
• Assessment of oocyte developmental potential, nuclear and cytoplasmic maturation.
• Untargeted metabolomics analysis to identify metabolic disruptions.
• Measurement of reactive oxygen species (ROS) and mitochondrial activity.
• Annexin-V staining to detect apoptosis.

Main Results:

• Pemetrexed exposure significantly reduced the developmental ratio of oocytes.
• Both cytoplasmic and nuclear maturation of mouse oocytes were impaired.
• Metabolomics revealed significant disruptions in oocyte metabolic homeostasis, particularly in choline-methyl metabolism.
• Pemetrexed exposure led to increased ROS production and decreased mitochondrial activity.
• Annexin-V signaling indicated pemetrexed induces apoptosis in oocytes.

Conclusions:

• Pemetrexed exposure has detrimental effects on female fertility.
• The drug impairs oocyte quality by disrupting metabolic homeostasis and inducing oxidative stress and apoptosis.
• These findings highlight potential risks of pemetrexed treatment for female reproductive health.