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Expression of Hypoxia-Inducible Factor1-α in Varicocele Disease: a Comprehensive Systematic Review

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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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Authors and Affiliations

  1. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

    Atefeh Babaei & Reza Asadpour

  2. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Parastar St., Daneshghah Blvd., P. O. Box 67155-1616, Kermanshah, Iran

    Atefeh Babaei, Sajjad Moradi, Zohreh Hoseinkhani & Kamran Mansouri

  3. Department of Molecular Medicine, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Davood Rezazadeh

  4. Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Sadat Dokaneheifard

  5. College of Materials Science and Engineering, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, Nanshan District Key Lab. for Biopolymers and Safety Evaluation, Shenzhen University, Shenzhen, 518060, People’s Republic of China

    Gaurav Sharma

  6. School of Chemistry, Shoolini University, Himachal Pradesh, Solan, 173212, India

    Gaurav Sharma

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  1. Atefeh Babaei
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  2. Sajjad Moradi
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  8. Kamran Mansouri
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Contributions

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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Correspondence to Kamran Mansouri.

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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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