The Impact of Diabetes Mellitus‐Related Oxidative Stress on Male Fertility: A Review
Simon Mwaringa Dena, Adesola Oluwaseun Adeleye, Kutullo Mohlala, Bridget Cebisile Langa, Chinyerum S. Opuwari
Abstract
Diabetes mellitus (DM) significantly impairs male reproductive health, largely through hyperglycemia-induced oxidative stress (OS). Elevated glucose activates detrimental metabolic pathways, notably the polyol pathway, which depletes antioxidant defenses and generates reactive oxygen species (ROS). This oxidative burden damages spermatozoa, leading to reduced motility, abnormal morphology, DNA fragmentation, and disrupted membrane integrity. OS also compromises the hypothalamic-pituitary-gonadal axis, lowering testosterone synthesis and impairing spermatogenesis. The formation of advanced glycation end products (AGEs) and chronic inflammation further exacerbate Leydig and Sertoli cell dysfunction, microvascular injury, and testicular apoptosis. Clinical evidence consistently links DM to deteriorated semen parameters, hormonal imbalances, and reduced natural conception rates, with poorer outcomes in assisted reproductive technologies. Obesity and metabolic syndrome, common comorbidities in DM, amplify oxidative stress and further impair fertility potential. While seminal plasma contains enzymatic and non-enzymatic antioxidants, these defenses are often insufficient in diabetic men. Targeted interventions, including antioxidant therapy, lifestyle modifications, glycemic control, and management of comorbidities, offer promise in mitigating oxidative damage. This review synthesizes current evidence on the molecular, endocrine, and clinical consequences of DM-related oxidative stress on male fertility, underscoring the need for integrated management strategies to preserve reproductive function in diabetic men.