Systemic impacts of diabetes on spermatogenesis and intervention strategies: multilayered mechanism analysis and cutting-edge therapeutic approaches

Diabetes mellitus (DM), a chronic metabolic disease with a high global prevalence, has increasingly been recognized for its adverse effects on the male reproductive system, particularly spermatogenesis. This review systematically summarizes the multifaceted impacts of diabetes on spermatogenesis, encompassing molecular mechanisms such as oxidative stress, endocrine disruption, dysregulated gene expression, metabolic imbalance, apoptosis, microcirculation impairment, and chronic inflammation, as revealed by recent studies. The intricate effects of these mechanisms on sperm quality, reproductive function, and offspring health are also thoroughly explored. A key innovation of this review lies in integrating recent advances, especially those highlighting the roles of epigenetic modifications, mitochondrial dysfunction, and insulin resistance (IR)-related pathways in spermatogenesis. Furthermore, the review evaluates the potential of personalized interventions, including glycemic control, antioxidant therapies, and lifestyle modifications, providing a scientific foundation for the development of more effective preventive and therapeutic strategies. This comprehensive analysis offers forward-looking guidance for future research and clinical interventions addressing diabetes-associated male infertility.