Proteomic analysis for busulfan-induced spermatogenesis disorder.

Area of Science:

• Proteomics
• Toxicology
• Reproductive Biology

Background:

• Busulfan is a key drug for chronic myelogenous leukemia and stem cell transplantation.
• Busulfan can cause reproductive and immune system damage.
• Limited data exists on protein expression changes in busulfan-treated testes.

Purpose of the Study:

• To investigate the proteomic changes in busulfan-induced spermatogenesis disorder.
• To identify key proteins and pathways affected by busulfan exposure.
• To establish a timeline for testicular recovery after busulfan treatment.

Main Methods:

• Utilized a busulfan-induced mouse model of spermatogenesis disorder.
• Performed label-free quantitative proteomics analysis on testicular tissue.
• Conducted clustering heatmap, Gene Ontology, KEGG pathway, and protein-protein interaction analyses.
• Validated findings using molecular experiments like Western blotting.

Main Results:

• Busulfan treatment led to abnormal testicular morphology, reduced sperm count, and decreased testis weight.
• Proteomics identified 190 significantly downregulated proteins, including LDHAL6B and USP7, at 30 days post-treatment.
• Testicular function and sperm parameters showed progressive improvement from 70 to 80 days.
• Western blotting confirmed dynamic changes in LDHAL6B protein levels correlating with recovery.

Conclusions:

• Identified 190 downregulated proteins and established 70 days as a recovery cut-off point for busulfan-induced testicular damage.
• Enhanced understanding of busulfan's reproductive toxicity in a mouse model.
• Findings aid in preventing and treating busulfan-related reproductive disorders.