Extended adverse effects of cyclophosphamide on mouse ovarian function

Area of Science:

• Reproductive biology
• Oncology
• Toxicology

Background:

• Cancer treatments like chemotherapy can impair reproductive health.
• Increased cancer survival rates necessitate addressing fertility issues in survivors.
• Cyclophosphamide (Cy) is a common chemotherapeutic agent with known reproductive toxicity.

Purpose of the Study:

• To investigate the pathophysiological effects of multiple cyclophosphamide exposures on mouse ovaries.
• To elucidate the molecular mechanisms underlying chemotherapy-induced ovarian damage.

Main Methods:

• Female mice received six intraperitoneal injections of cyclophosphamide over two weeks.
• Ovaries, sera, and oocytes were collected for histological, hormonal, and quality assessments.
• Gene expression analysis using microarray and bioinformatics identified molecular changes in ovaries.

Main Results:

• Cyclophosphamide exposure led to decreased anti-Müllerian hormone levels.
• Follicle loss and impaired oocyte quality were observed and found to be irreversible.
• Sustained alterations in genes related to folliculogenesis and oogenesis persisted post-treatment.

Conclusions:

• Adverse effects of cyclophosphamide on ovarian function and oocytes are long-lasting, even after chemotherapy cessation.
• Strategies are needed to prevent ovarian damage or restore function in cancer survivors.
• Safeguarding fertility is essential for young cancer survivors undergoing chemotherapy.