Hypoxia pathway has more impact than inflammation pathway on etiology of infertile men with varicocele

Andrologia. 2019 Mar;51(2):e13189. doi: 10.1111/and.13189. Epub 2018 Nov 26.

Abstract

This study aimed to compare main molecular markers of hypoxia (HIF1-α and P53) and inflammation (TLR-2, TLR-4 and TNF-α) pathways between infertile men with varicocele and fertile individuals. Sperm parameters such as sperm concentration, motility and morphology were assessed according to World Health Organization (Laboratory manual for the examination and processing of human semen. Geneva, Switzerland, 2010) guideline in 20 infertile men with grade II or III varicocele, and 20 fertile men candidate of family balancing. In addition, sperm DNA fragmentation and molecular markers involved in hypoxia and inflammation pathways were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and real-time PCR respectively. Mean of sperm parameters (concentration, motility and morphology) and DNA integrity were significantly lower in infertile men with varicocele compared to fertile individuals. Unlike markers involved in inflammation pathway, mean expression of markers of hypoxia pathway (HIF1-α and P53) was significantly higher in infertile men with varicocele compared to fertile individuals (p < 0.05), and also a significant correlation was observed between expression of HIF1-α and P53 (r = 0.461; p = 0.003). Overall, the result of this study suggests higher likelihood of involvement of hypoxia pathway, in comparison with inflammation pathway, in pathogenesis varicocele associated with male infertility.

Keywords: DNA fragmentation; hypoxia; inflammatory; sperm parameters; varicocele.

MeSH terms

  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Cell Shape / physiology
  • DNA Fragmentation
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Infertility, Male / etiology*
  • Infertility, Male / metabolism
  • Inflammation / metabolism*
  • Male
  • Semen Analysis
  • Sperm Count
  • Sperm Motility / physiology
  • Spermatozoa / cytology
  • Spermatozoa / metabolism*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Varicocele / complications*
  • Varicocele / metabolism

Substances

  • Biomarkers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha

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