Download fulltext HTML
Fallah Asl, H., Jalali Mashayekhi, F., Zendedel, A., & Baazm, M. (2023). The time course of nod-like receptor family pyrin domain containing 3 inflammasome complex expressions in the testis tissue of an experimental varicocele rat model: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 21(7), 577–584. https://doi.org/10.18502/ijrm.v21i7.13895

https://doi.org/10.18502/ijrm.v21i7.13895

statistics

  • 143 Abstract Views
  • 39 PDF Views
  • 0 HTML Views

authors

  • Hamideh Fallah Asl

    Hamideh Fallah Asl

    Students Research Committee, Arak University of Medical Sciences, Arak, Iran.
  • Farideh Jalali Mashayekhi

    Farideh Jalali Mashayekhi

    Department of Genetics and Biochemistry, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
  • Adib Zendedel

    Adib Zendedel

    Institute of Neuroanatomy, Uniklinik RWTH Aachen, 52074 Aachen, Germany.
  • Maryam Baazm

    Maryam Baazm

    Department of Anatomy, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

Published Date

  • Aug 19, 2023

The time course of nod-like receptor family pyrin domain containing 3 inflammasome complex expressions in the testis tissue of an experimental varicocele rat model: An experimental study

International Journal of Reproductive BioMedicine (IJRM) / International Journal of Reproductive BioMedicine (IJRM): Volume 21, Issue No. 7 / Pages 577–584

Abstract

Background: Varicocele is characterized by abnormal dilation of the testicular vein, which results in hypoxia, the accumulation of reactive oxygen species, and the production of proinflammatory cytokines. It seems that a group of cytosolic receptors named nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, is activated and involved in the pathogenesis of varicocele.


Objective: We aim to determine the time course of NLRP3 inflammasome expression in the testis tissue following varicocele induction.


Materials and Methods: In this experimental study, 36 adult Wistar rats (8 wk 200-250 gr) were used. For the varicocele induction, the left renal vein was partially ligated. The mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 were evaluated by real-time polymerase chain reaction at 1, 2, 4, 8, and 12 wk after varicocele induction.


Results: Results showed that the gene expression of NLRP3 inflammasome component including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 did not alter during wk 1, 2, 4, and 8 after operation (p = 0.09). 12 wk after varicocele induction, gene expression levels were significantly unregulated (p = 0.02).


Conclusion: Our data provides clear evidence that varicocele stimulates inflammasome activation in the testis tissue 12 wk after the operation, and this time is required for investigating NLRP3 activity in the varicocele rat model.


Key words: Varicocele, Inflammasomes, NLRP3, Rat.

References
[1] Finelli R, Leisegang K, Kandil H, Agarwal A. Oxidative stress: A comprehensive review of biochemical, molecular, and genetic aspects in the pathogenesis and management of varicocele. World J Men’s Health 2022; 40: 87-103.

[2] Hassanin AM, Ahmed HH, Kaddah AN. A global view of the pathophysiology of varicocele. Andrology 2018; 6: 654-661.

[3] Fang Y, Su Y, Xu J, Hu Z, Zhao K, Liu C, et al. Varicocele-mediated male infertility: From the perspective of testicular immunity and inflammation. Front Immunol 2021; 12: 729539.

[4] Reddy SVK, Shaik AB. Effect of varicocele treatment on conventional semen analysis. Esteves SC, Cho C-L, Majzoub A, Agarwal A. Varicocele and male infertility: A complete guide. Switzerland: Springer; 2019: 255-269.

[5] Caseley EA, Poulter JA, Rodrigues F, Immunome Project Consortium for Autoinflammatory Disorders (ImmunAID), McDermott MF. Inflammasome inhibition under physiological and pharmacological conditions. Genes Immun 2020; 21: 211-223.

[6] Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol 2021; 18: 2114-2127.

[7] Baazm M, Ghafarizadeh AA, Noshad Kamran AR, Beyer C, Zendedel A. Presence of the NLRP3 inflammasome components in semen of varicocele patients. Int J Fertil Steril 2020; 14: 46-50.

[8] Moretti E, Signorini C, Noto D, Tripodi SA, Menchiari A, Sorrentino E, et al. Seminal levels of omentin- 1/ITLN1 in inflammatory conditions related to male infertility and localization in spermatozoa and tissues of male reproductive system. J Inflamm Res 2022; 15: 2019-2031.

[9] Al-Harbi NY. Resistin, leptin in human seminal plasma: Relationship with TNF-Α and parameters semen in oligozoospermia with and without varicocele. Eur J Mol Clin Med 2020; 7: 4838- 4846.

[10] Habibi B, Seifi B, Mougahi SM-HN, Ojaghi M, Sadeghipour HR. Increases in interleukin-6 and interferon-gamma levels is progressive in immature rats with varicocele. Ir J Med Sci 2015; 184: 531-537.

[11] Minutoli L, Antonuccio P, Irrera N, Rinaldi M, Bitto A, Marini H, et al. NLRP3 inflammasome involvement in the organ damage and impaired spermatogenesis induced by testicular ischemia and reperfusion in mice. J Pharmacol Exp Ther 2015; 355: 370-380.

[12] Milner MT, Maddugoda M, Götz J, Burgener SS, Schroder K. The NLRP3 inflammasome triggers sterile neuroinflammation and Alzheimer’s disease. Curr Opini Immunol 2021; 68: 116-124.

[13] Zendedel A, Johann S, Mehrabi S, Joghataei MT, Hassanzadeh Gh, Kipp M, et al. Activation and regulation of NLRP3 inflammasome by intrathecal application of SDF-1a in a spinal cord injury model. Mol Neurobiol 2016; 53: 3063-3075.

[14] Ibrahim E, Aballa TC, Lynne CM, Brackett NL. Oral probenecid improves sperm motility in men with spinal cord injury. J Spinal Cord Med 2018; 41: 567- 570.

[15] Hajipour E, Mashayekhi FJ, Mosayebi G, Baazm M, Zendedel A. Resveratrol decreases apoptosis and NLRP3 complex expressions in experimental varicocele rat model. Iran J Basic Med Sci 2018; 21: 225-229.

[16] Antonuccio P, Micali AG, Romeo C, Freni J, Vermiglio G, Puzzolo D, et al. NLRP3 inflammasome: A new pharmacological target for reducing testicular damage associated with varicocele. Int J Mol Sci 2021; 22: 1319.

[17] Turner TT. The study of varicocele through the use of animal models. Hum Reprod Update 2001; 7: 78-84.

[18] Camargo M, Ibrahim E, Intasqui P, Belardin LB, Antoniassi MP, Lynne CM, et al. Seminal inflammasome activity in the adult varicocele. Hum Fertil 2022; 25: 548-556.

[19] Lammerding L, Slowik A, Johann S, Beyer C, Zendedel A. Poststroke inflammasome expression and regulation in the peri-infarct area by gonadal steroids after transient focal ischemia in the rat brain. Neuroendocrinology 2016; 103: 460-475.

[20] Bernstein AP, Najari BB. Varicocele treatment and serum testosterone. Androgens: Clin Res Ther 2022; 3: 133-137.

[21] Ghandehari-Alavijeh R, Tavalaee M, Zohrabi D, Foroozan-Broojeni Sh, Abbasi H, Nasr-Esfahani MH. Hypoxia pathway has more impact than inflammation pathway on etiology of infertile men with varicocele. Andrologia 2019; 51: e13189.

[22] Gao L, Dong Q, Song Z, Shen F, Shi J, Li Y. NLRP3 inflammasome: A promising target in ischemic stroke. Inflamm Res 2017; 66: 17-24.

[23] Hong P, Gu R-N, Li F-X, Xiong X-X, Liang WB, You Z-J, et al. NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes. J Neuroinflammation 2019; 16: 121.

[24] Baazm M, Behrens V, Beyer C, Nikoubashman O, Zendedel A. Regulation of inflammasomes by application of omega-3 polyunsaturated fatty acids in a spinal cord injury model. Cells 2021; 10: 3147.

[25] Jiang W, Li M, He F, Zhou S, Zhu L. Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice. J Neuroinflammation 2017; 14: 207.

[26] Sharma A, Choi JS, Stefanovic N, Al-Sharea A, Simpson DS, Mukhamedova N, et al. Specific NLRP3 inhibition protects against diabetes-associated atherosclerosis. Diabetes 2021; 70: 772-787.