Optimizing a Male Reproductive Aging Mouse Model by D-Galactose Injection

Area of Science:

• Reproductive Biology
• Aging Research
• Toxicology

Background:

• The d-galactose (d-gal) animal model is widely used for aging research, accelerating aging in various organs.
• However, its application in studying male reproductive aging and spermatogenesis remains underexplored.
• This study addresses the need for a reliable model to investigate d-gal-induced male reproductive senescence.

Purpose of the Study:

• To optimize a d-galactose-induced animal model for studying male reproductive aging in mice.
• To investigate the underlying mechanisms of accelerated senescence during spermatogenesis induced by d-gal.
• To identify key genes affected during d-gal-induced male reproductive aging.

Main Methods:

• Male C57Bl/6 mice received daily intraperitoneal injections of vehicle control or d-galactose (100 or 200 mg/kg) for six or eight weeks.
• Evaluated oxidative stress markers (superoxide dismutase activity, lipid peroxidation) and reproductive parameters (testis weight/body weight ratio, sperm count, sperm motility, sperm morphology).
• Utilized cDNA microarray analysis to compare testicular gene expression profiles between d-gal-treated and control groups.

Main Results:

• D-galactose administration significantly decreased superoxide dismutase activity and increased lipid peroxidation in serum and testes.
• Treated mice showed reduced testis weight/body weight ratio, decreased sperm count, and increased percentages of immotile and abnormal sperm.
• Microarray analysis revealed significant up- or down-regulation of nine spermatogenesis-related genes, including those critical for sperm morphology and nuclear integration.

Conclusions:

• The d-galactose-injected mouse model effectively replicates key aspects of male reproductive aging, including oxidative stress and impaired spermatogenesis.
• The observed changes in gene expression provide insights into the molecular mechanisms underlying d-gal-induced reproductive senescence.
• This optimized model is suitable for further research into the causes and potential interventions for male reproductive aging.