Diabetes and male infertility: A review of sperm chromatin damage and epigenetic effects

Diabetes mellitus (DM) is a global health concern impacting male fertility through detrimental effects on sperm chromatin structure and DNA integrity. This review discusses how DM impairs spermatogenesis, primarily through the induction of oxidative stress, which can result in significant DNA fragmentation and compromised chromatin integrity in spermatozoa. We examine evidence suggesting that even men with seemingly normal semen parameters might exhibit hidden sperm DNA damage if diabetic. The reviewed literature consistently reports elevated sperm DNA fragmentation indices and increased susceptibility to denaturation in diabetic men compared to healthy controls. Furthermore, the potential for paternal diabetes to influence offspring health through epigenetic modifications in sperm DNA is discussed. Studies in animal models and human subjects indicate alterations in sperm DNA methylation patterns and microRNA content, suggesting a plausible mechanism for the transgenerational transmission of metabolic traits. Finally, the review examines the potential benefits of diabetes treatment in improving sperm parameters and chromatin integrity. Evidence from clinical studies demonstrates that interventions, particularly intensive glycemic control, can lead to measurable improvements in sperm DNA integrity. A comprehensive search was conducted in major scientific databases, including PubMed, Scopus, and Web of Science, to identify studies examining the impact of DM on male fertility using keywords like "diabetes mellitus", "male infertility", "sperm chromatin structure", "DNA fragmentation", and "epigenetics". This review addresses the critical issue of how DM negatively impacts male fertility by altering sperm chromatin structure and DNA integrity. We explore the potential mechanisms involved and the impact of diabetes treatment on sperm quality. Additionally, the emerging concept of epigenetic inheritance and its potential role in this context is discussed.