Varicocoele and oxidative stress: New perspectives from animal and human studies

Andrology. 2021 Mar;9(2):546-558. doi: 10.1111/andr.12940. Epub 2020 Dec 6.


Background: Varicocoele (VCL), one of the main causes of male subfertility, negatively affects testicular function. Due to limited access to human testicular tissue, animal model studies have been used to evaluate molecular and, recently, epigenetic changes attributed to pathophysiology induced by VCL.

Objectives: This review aims to provide an update on the latest findings regarding the link between VCL-induced biochemical stress and molecular changes in germ cells and spermatozoa. Endocrine and antioxidant status, testicular chaperone-specific hemostasis failure, altered testicular ion balance, metabolic disorders, and altered carbon cycling during spermatogenesis are among the many features that will be presented.

Discussion: Literature review coupled with our own findings suggests that ionic imbalance, hypoxia, hyperthermia, and altered blood flow could lead to severe chronic oxidative and nitrosative stress in patients with VCL leading to defective spermatogenesis and impairment of the integrity of all sperm cell components and compartments down to the epigenetic information they carry.

Conclusion: Since oxidative stress is an important feature of the reproductive pathology of VCL, therapeutic strategies such as the administration of appropriate antioxidants could be undertaken as a complementary non-invasive treatment line.

Keywords: chaperones; global methylation; ion balance; nitrosative stress; oxidative stress; varicocoele.

Publication types

  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic
  • Heat-Shock Response
  • Humans
  • Ions / metabolism
  • Male
  • Nitrogen / metabolism
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism
  • Testis / metabolism
  • Varicocele / genetics
  • Varicocele / metabolism*


  • Ions
  • Reactive Oxygen Species
  • Nitrogen