Abstract
Hypoxia has been suggested as an important pathophysiological feature in varicocele disease. On the other hand, the expression of hypoxia-inducible factor 1-alpha (HIF1-α) is associated with the incidence of hypoxia. In this study, we investigated the expression of HIF1-α in varicocele disease through a comprehensive systematic review. We searched PubMed, Scopus, Web of Science, and Embase databases to identify the related studies published up to February 2021. Human studies have demonstrated an increase in the HIF-1α protein expression in the internal spermatic vein (ISV) of the varicocele testicle. HIF-1α mRNA expression in the seminal plasma was significantly higher in infertile varicocele patient compared with fertile ones. Similarly, most animal studies demonstrated a significant increase in HIF-1α gene and protein expression in varicocele testicular tissue compared with control groups. The studies illustrated that hypoxia followed by increased expression of hypoxia-inducible factor 1-alpha (HIF1-α) mRNA and protein occurs in varicocele disease. Expression of HIF-1α regulates the expression of many genes, including VEGF, p53, GLUT, Bax, and Caspase-3, that could be involved in many of the varicocele pathophysiological effects such as DNA fragmentation and apoptosis of sperm cells. Further studies with a large number of patients are necessary and can provide more definitive evidence.
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Abbreviations
- AI:
-
Apoptosis index
- bHLH:
-
Basic helix-loop-helix
- BV:
-
Brachial vein
- CTGF:
-
Connective tissue growth factor
- ELISA:
-
Enzyme-linked immunosorbent assay
- H&E:
-
Hematoxylin and eosin staining
- HIF1-α:
-
Hypoxia-inducible factor 1-alpha
- HIFs:
-
Hypoxia-inducible factors
- HREs:
-
Hypoxia response elements
- ISV:
-
Internal spermatic vein
- MeSHs:
-
Medical subject heading
- ODD:
-
Oxygen-dependent degradation domain
- PHD:
-
Hypoxia, prolyl hydroxylase
- PRISMA:
-
Preferred Reported Cases for Systematic Reviews and Meta-Analyzes
- pVHL:
-
Von Hippel-Lindau protein
- ROM:
-
Reactive oxygen metabolite
- ROS:
-
Reactive oxygen species
- RT-qPCR:
-
Real-time polymerase chain reaction
- TUNEL:
-
Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling
- VEGF:
-
Vascular endothelial growth factor
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A.B. designed the study; Z.H and D.R. conducted the publication search and revised manuscript; A.B., S.M., and K.M. wrote the paper and revised the manuscript; S.D. and G.S. edited the paper; K.M. was primary responsible for the final content. All authors read and approved the final manuscript.
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Babaei, A., Moradi, S., Hoseinkhani, Z. et al. Expression of Hypoxia-Inducible Factor1-α in Varicocele Disease: a Comprehensive Systematic Review. Reprod. Sci. 29, 2731–2743 (2022). https://doi.org/10.1007/s43032-021-00696-y
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DOI: https://doi.org/10.1007/s43032-021-00696-y