Adriamycin induced spermatogenesis defect is due to the reduction in epididymal adipose tissue mass: a possible hypothesis.

Adriamycin is an anthracycline antibiotic used as anticancer drug since past few decades. Though effective against cancer, it is cardiotoxic, nephrotoxic, hepatotoxic and also toxic for reproductive system. Although a number of potential toxic mechanisms have been identified following exposure to adriamycin, the major pathogenic mechanism appears to be the generation of toxic reactive oxygen species (ROS). Animals treated with adriamycin have shown a decrease in total sperm count. This implies that adriamycin impairs the process of spermatogenesis. Epididymal white adipose tissue (EWAT) is necessary for normal spermatogenesis, and decrease in the EWAT causes disturbance in spermatogenesis. Factor X is an unknown molecule synthesized by EWAT that plays crucial role in spermatogenesis. Adriamycin inhibits Kruppel-like factor 4 (KLF-4) and thus downregulates the adipogenesis process needed to maintain the EWAT mass. Apart form adipocytes, KLF-4 and peroxisome proliferator-activated receptor gamma (PPAR-γ) are also found in spermatogonium and testis, implying its vital role in spermatogenesis. Adriamycin treatment inhibits KLF-4 and thus PPAR-γ in EWAT and spermatogonium. Reduction of EWAT might cause a decrease in Factor X level. Declining of Factor X level, KLF-4 and PPAR-γ together will lead to disturbance in spermatogenesis process.