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Insight into oxidative stress in varicocele-associated male infertility: part 1

Nature Reviews Urology volume 9, pages 678–690 (2012)Cite this article

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Abstract

Varicocele is recognized as the leading cause of male infertility because it can impair spermatogenesis through several distinct pathophysiological mechanisms. Current evidence supports oxidative stress as a key element in the pathophysiology of varicocele-related infertility, although these mechanisms have not yet been fully described. Measurement of the reactive oxygen species and other markers of oxidative stress, including the levels of the antioxidant enzymes catalase and superoxide dismutase, can provide valuable information on the extent of oxidative stress and might guide therapeutic management strategies. The testis can respond to varicocele-associated cell stressors, such as heat stress, ischaemia or production of vasodilators (for example, nitric oxide) at the expense of the generation of excessive reactive oxygen species. These responses have their own implications in exacerbating the underlying oxidative stress and on the subsequent infertility.

Key Points

  • Oxidative stress is a key element in the pathophysiology of varicocele-related infertility and several mechanisms by which this operates have been studied but have not yet been fully described

  • Although small quantities of reactive oxygen species (ROS) have important roles in sperm function, a disproportionate increase in ROS usually leads to oxidative stress

  • Heat stress, hypoxia, reflux of adrenal and renal metabolites and hormonal disturbances have all been proposed as mechanisms to explain the pathophysiological effects of varicocele on testicular function

  • Several intrinsic mechanisms are available—including the antioxidant enzymes catalase or superoxide dismutase—that counteract the actions of ROS; disruption of these protective antioxidants can also lead to oxidative stress

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Figure 1: Reactive oxygen and nitrogen species generation in infertile men with varicocele.
Figure 2: Varicocele-induced sperm biochemical pathways of ROS generation.

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Acknowledgements

The authors are supported in part by research funds from the Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, OH, USA.

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Authors and Affiliations

  1. Center for Reproductive Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Ashok Agarwal & Alaa Hamada

  2. ANDROFERT, Referral Center for Male Reproduction, Campinas, 13075-460, SP, Brazil

    Sandro C. Esteves

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  1. Ashok Agarwal
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A. Hamada researched the data for the article and wrote the manuscript. All authors contributed to the discussion of the article content and edited the manuscript before submission.

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Agarwal, A., Hamada, A. & Esteves, S. Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat Rev Urol 9, 678–690 (2012). https://doi.org/10.1038/nrurol.2012.197

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