Diabetes-Induced Impairments in Male Reproductive Function

Diabetes mellitus exerts multifaceted detrimental effects on male reproductive health, encompassing hormonal, cellular and vascular dimensions. Chronic hyperglycaemia triggers an imbalance between pro-oxidant and antioxidant systems, leading to oxidative stress, inflammation and accumulation of advanced glycation end-products within the testes. Leydig cells show reduced steroidogenesis and diminished testosterone synthesis, while Sertoli cell function is compromised, impairing the supportive niche required for spermatogenesis. Disruption of the hypothalamic–pituitary–gonadal axis further perturbs gonadotropin release, exacerbating germ cell loss, tubule atrophy and poor semen quality. Microcirculatory defects, driven by impaired vascular endothelial growth factor signalling and endothelial dysfunction, restrict nutrient delivery and oxygenation, contributing to testicular atrophy. At the molecular level, dysregulated autophagy, ferroptosis and activation of stress-responsive kinases undermine cellular homeostasis in both germ and somatic cells. Collectively, these processes result in reduced sperm count, motility and viability, elevated DNA fragmentation and altered sperm morphology. The global rise in diabetes incidence underscores the significance of these impairments for male fertility, prompting exploration of targeted antioxidant therapies, metabolic modulators and lifestyle interventions to preserve reproductive function.

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Diabetes-Induced Impairments in Male Reproductive Function publication trend

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Technical terms

Oxidative stress: An imbalance between reactive oxygen species production and antioxidant defences, leading to cellular damage.

Advanced glycation end-products (AGEs): Harmful compounds formed by non-enzymatic reactions between sugars and proteins or lipids, implicated in vascular and tissue injury.

Leydig cell: A testicular somatic cell type responsible for testosterone synthesis under luteinising hormone stimulation.

Sertoli cell: A supportive testicular cell that nurtures developing germ cells and maintains the blood–testis barrier.

Autophagy: A regulated intracellular process that degrades damaged organelles or proteins to maintain cellular homeostasis.

Ferroptosis: A form of regulated cell death driven by iron-dependent lipid peroxidation and oxidative imbalance.

References

1. Cardiac-derived CTRP9 mediates the protection of empagliflozin against diabetes-induced male subfertility in mice. Clinical Science (2024).
2. Diabetes-induced male infertility: potential mechanisms and treatment options. Molecular Medicine (2024).
3. Diabetes‐Induced Autophagy Dysregulation Engenders Testicular Impairment via Oxidative Stress. Oxidative Medicine and Cellular Longevity (2023).
4. Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget (2018).