Impact of aging on spermatogenic function and reproductive outcomes in repro57 heterozygous male mice: A model for age-related infertility.

PURPOSE: This study aims to investigate the histological changes, sperm parameters, and their impact on embryo development rates and offspring numbers in advanced-age male repro57 heterozygous mice, corresponding to approximately 40 years of age in humans. METHODS: Sperm parameters were assessed in both young and advanced-age repro57 heterozygous mice, as well as in young and advanced-age wild-type mice. Additionally, testis weight and histological analysis of seminiferous tubules were conducted to identify degenerative changes. Male mice from each group were mated with young wild-type females to compare offspring numbers, and in vitro fertilization (IVF) was used to evaluate fertilization and blastocyst formation rates. RESULTS: No significant differences in sperm concentration and motility were observed between young and aged wild-type mice or between young wild-type and young repro57 heterozygous mice. However, advanced-age repro57 heterozygous mice exhibited significantly lower sperm parameters and testis weight compared to advanced-age wild-type mice. Histological analysis revealed increased Sertoli cell vacuolation in the seminiferous tubules of advanced-age repro57 heterozygous mice. Additionally, these advanced-age mice exhibited significantly lower blastocyst formation rates and produced fewer offspring compared to advanced-age wild-type mice. CONCLUSION: Advanced reproductive aging in repro57 heterozygous male mice is associated with marked senescence-like degenerative changes, leading to a decline in offspring numbers, attributed to increased Sertoli cell vacuolation and diminished sperm quality.