NEW RESEARCH has shown that sustained testicular hypoxia, caused by conditions such as sleep apnoea and varicocele, poses a significant risk to male fertility, with potential intergenerational consequences.
Male infertility has become an increasing concern, with sperm counts declining over the past 50 years. A recent review, highlights the role of testicular hypoxia—low oxygen availability in the testes—as a contributing factor. Conditions such as sleep apnoea, varicocele, and high-altitude exposure can lead to hypoxia, affecting sperm production, hormone regulation, and reproductive health. Despite the prevalence of these conditions, their cumulative impact on fertility remains incompletely understood. Researchers are now calling for greater clinical awareness and management strategies to mitigate these risks.
The review analysed multiple studies investigating hypoxia-induced subfertility. Findings indicate that testicular hypoxia can directly affect sperm quality by disrupting gene expression, increasing oxidative stress, and altering endocrine function. Notably, varicocele—a condition characterised by enlarged veins in the scrotum—accounts for up to 45% of male infertility cases. Similarly, obstructive sleep apnoea, which affects 13%–30% of men and is rising due to increasing obesity rates, has been correlated with reduced sperm quality. Studies on hypobaric hypoxia, mimicking high-altitude exposure, reveal temporary but significant declines in sperm function, though recovery is possible once normal oxygen levels are restored. Alarmingly, emerging evidence suggests that paternal hypoxia exposure may influence embryo development and even have transgenerational effects on fertility and offspring health.
These findings underscore the urgent need for heightened clinical vigilance in recognising and treating conditions associated with testicular hypoxia. Early diagnosis and management of varicocele and sleep apnoea could significantly improve fertility outcomes. While testicular stem cells exhibit resilience and some hypoxia-induced infertility may be reversible, further research is necessary to understand long-term and intergenerational impacts. Given the decline in male fertility rates, prioritising studies on the molecular mechanisms of hypoxia and developing targeted interventions could be crucial in safeguarding reproductive health for future generations.
Katrina Thornber, EMJ
Reference
Lord T. Pathophysiological effects of hypoxia on testis function and spermatogenesis. Nat Rev Urol. 2025;DOI:10.1038/s41585-024-00969-6.
