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Diabetes-driven oxidative stress and calcium dysregulation in gametogenesis and early fertilization
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2026
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1-s2.0-S1056872726000905-main.pdf
Adobe PDF, 2.69 MB
- Embargoed until 2027-05-22
Abstract
Diabetes mellitus is associated with chronic hyperglycemia, metabolic instability and systemic oxidative stress, all of which adversely affect reproductive function in both males and females. Increasing evidence indicates that sustained reactive oxygen species (ROS) production and disrupted intracellular calcium (Ca2+) signaling represent central mechanisms linking diabetes to impaired gametogenesis and early fertilization failure. In both oocytes and spermatozoa, oxidative stress and Ca2+ dysregulation promote mitochondrial dysfunction, DNA damage, defective chromatin remodeling and increased apoptotic susceptibility. These alterations compromise meiotic progression, reduce gamete competence and impair the highly coordinated Ca2+-dependent events required for fertilization and early embryonic development. Emerging studies further suggest that diabetes-related microvascular injury, hormonal imbalance and local inflammatory signaling exacerbate oxidative and Ca2+-mediated disturbances within reproductive tissues. Disruption of antioxidant defense systems, impaired mitochondrial quality control and altered Ca2+-handling machinery collectively create a maladaptive intracellular environment that undermines reproductive capacity. This review integrates molecular, experimental and clinical evidence supporting a central role for the ROS-Ca2+–mitochondrial axis in diabetic reproductive dysfunction. We also discuss evolving therapeutic strategies, including targeted antioxidants, Ca2+-modulating agents and molecular interventions that aim to restore redox and Ca2+ homeostasis. Understanding these intersecting pathways may identify novel translational targets to improve fertility outcomes in patients with diabetes. © 2026 The Authors.