Iranian Journal of Veterinary Surgery

Iranian Journal of Veterinary Surgery

Protective Effects of Ellagic Acid on Oxidative Stress and in vitro Fertilization in a Murine Model of Varicocele

Document Type : Original Article

Authors
Noor Noori-Abd 1
Gholamreza Najafi-Tazekand 2
Ali Shalizar-Jalali 2
Khalid Yassen Zakair Al-Zamily 3
Siamak Ghabeli-Zaherkandi 1
1 PhD Candidate, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
2 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
3 Kut Technical Institute, Middle Technical University, Baghdad, Iraq.
10.30500/ivsa.2024.484177.1420
Abstract
Varicocele is defined by abnormal tortuosity and pampiniform plexus veins dilation within the spermatic cord and is the most common surgically correctible cause of male infertility. This study aimed to evaluate the protective effect of ellagic acid (EL) on sperm parameters and in vitro fertilization (IVF) in a murine model of varicocele. In this experimental study, 50 mature male mice were randomly divided into five groups (n = 10), including control, varicocele, varicocele with a low dose of EL (25 mg/kg), varicocele with a medium dose of EL (50 mg/kg), and varicocele with a high dose of EL (100 mg/kg). After a 28-day treatment period, malondialdehyde, total anti-oxidant capacity (TAC), sperm parameters, and IVF were evaluated. In the varicocele group, TAC, and sperm count, motility, and viability, as well as zygotes, two-cell embryos, blastocysts, and hatched embryos were significantly reduced compared to the control group. Ellagic acid administration improved sperm parameters, fertilization rate, and embryo development. These findings suggest that EL owing to its anti-oxidant and free radicals scavenging abilities can inhibit the damaging effects of varicocele on fertility in mice.
Keywords
Ellagic acid
Varicocele
Sperm
In vitro fertilization
Mice
Subjects
  1. Kamal KM, Javeri K, Zini A. Microsurgical varicocelectomy in the era of assisted reproductive technology: influence of initial semen quality on pregnancy rates. Fertility and Sterility. 2001; 75(5): 1013-1016. doi: 10.1016/S0015-0282(01)01698-3
  2. Skoog SJ, Roberts KP, Goldstein M, Pryor JL. The adolescent varicocele: what’s new with an old problem in young patients? Pediatrics. 1997; 100(1): 112-121. doi: 10.1542/peds.100.1.112
  3. Benoff S, Gilbert BR. Varicocele and male infertility: part I. Preface. Human Reproduction Update. 2001; 7(1): 47-54. doi: 10.1093/humupd/7.1.47
  4. Agarwal A, Sharma RK, Desai NR, Prabakaran S, Tavares A, Sabanegh E. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009; 73(3): 461-469. doi: 10.1016/j.urology.2008.07.053
  5. Pasqualotto FF, Sobreiro BP, Hallak J, Pasqualotto EB, Lucon AM. Induction of spermatogenesis in azoospermic men after varicocele repair: an update. Fertility and Sterility. 2006; 85(3): 635-639. doi: 10.1016/j.fertnstert.2005.08.043
  6. Shiraishi K, Naito K. Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. Journal of Urology. 2007; 178 (3 Pt 1): 1012-1017. doi: 10.1016/j.juro.2007.05.027
  7. Smith R, Kaune H, Parodi D, Madariaga M, Rios R, Morales I, Castro A. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Human Reproduction. 2006; 21(4): 986-993. doi: 10.1093/humrep/dei429
  8. Moustafa MH, Sharma RK, Thornton J, Mascha E, Abdel-Hafez MA, Thomas AJ, Agarwal A. Relationship between ROS roduction, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility. Human Reproduction. 2004; 19(1): 129-138. doi: 10.1093/humrep/deh024
  9. Lin W, Liu G, Kang X, Guo P, Shang Y, Du R, Wang X, Chen L, Yue R, Kong F, Zhu Q. Ellagic acid inhibits high glucose-induced injury in rat mesangial cells via the PI3K/Akt/FOXO3a signaling pathway. Experimental and Therapeutic Medicine. 2021; 22(3): 1017. doi: 10.3892/etm.2021.10449
  10. Hamza R.Z, Al-Baqami NM. Testicular protective effects of ellagic acid on monosodium glutamate-induced testicular structural alterations in male rats. Ultrastructural Pathology. 2019; 43 (4-5): 170-183. doi: 10.1080/01913123.2019.1671569
  11. Dizakar SÖA, Saribas GS, Tekcan A. Effects of ellagic acid in the testes of streptozotocin induced diabetic rats. Drug and Chemical Toxicology. 2022; 45(5): 2123-2130. doi: 10.1080/01480545.2021.1908714
  12. Celik-Ozenci C, Bayram Z, Akkoyunlu G, Korgun ET, Erdogru T, Seval Y, Ustunel I, Baykara M, Demir R. Localization of NGF and nNOS in varicocele-induced rat testis. Acta Histochemica. 2006; 107(6): 435-442. doi: 10.1016/j.acthis.2005.10.001
  13. Azad F, Nejati V, Shalizar-Jalali A, Najafi G, Rahmani F. Royal jelly protects male mice against nicotine-induced reproductive failure. Veterinary Research Forum. 2018; 9(3): 231-238. doi: 10.30466/vrf.2018.32088
  14. Babaei M, Najafi G, Jalali AS, Behfar M. Effects of unilateral iatrogenic vas deferens trauma on fertility: an experimental in vitro fertilization mice model study. Bulletin of Emergency and Trauma. 2015; 3(4): 122-127.
  15. Armand Z, Najafi G, Farokhi F, Jalali AS. Attenuation of cyclosporine-induced sperm impairment and embryotoxicity by Crataegus monogyna fruits aqueous extract. Cell Journal. 2013; 15(3): 198-205.
  16. Mahdivand N, Najafi G, Nejati V, Shalizar-Jalali A, Rahmani F. Royal jelly protects male rats from heat stress-induced reproductive failure. Andrologia. 2019; 51(3): e13213. doi: 10.1111/and.13213.
  17. Aaly-Gharibeh Z, Hosseinchi M, Shalizar-Jalali A. Effect of nanocurcumin on fertility in murine model of polycystic ovary syndrome. Veterinary Research Forum. 2024; 15(2): 113-117. doi: 10.30466/vrf.2023.2006604.3935
  18. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as measure of "antioxidant power ": the FRAP as‌say. Analytical Biochemistry. 1996; 239(1): 70-76. doi: 10.1006/abio.1996.0292
  19. Belloli G, D’Agostino S, Pesce C, Fantuz E. Varicocele in childhood and adolescence and other testicular anomalies: an epidemiological study [Italian]. La Pediatria Medica e Chirurgica. 1993; 15(2): 159-162.
  20. Hauser R, Paz G, Botchan A, Yogev L, Yavetz H. Varicocele: effect on sperm functions. Human Reproduction Update. 2001; 7(5): 482-485. doi: 10.1093/humupd/7.5.482
  21. Wright EJ, Young GP, Goldstein M. Reduction in testicular temperature after varicocelectomy in infertile men. Urology. 1997; 50(2): 257-259. doi: 10.1016/s0090-4295(97)00191-x
  22. Fujisawa M, Hayashi A, Imanishi O, Tanaka H, Okada H, Matsumoto O, Kamidono S. The significance of gonadotropin-releasing hormone test for predicting fertility after varicocelectomy. Fertility and Sterility. 1994; 61(4): 779-782. doi: 10.1016/s0015-0282(16)56662-x
  23. Benoff SH, Millan C, Hurley IR, Napolitano B, Marmar JL. Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Human Reproduction. 2004; 19(3): 616-627. doi: 10.1093/humrep/deh139
  24. Li H, Dubocq F, Jiang Y, Tiguert R, Gheiler EL, Dhabuwala CB. Effect of surgically induced varicocele on testicular blood flow and Sertoli cell function. Urology. 1999; 53(6): 1258-1262. doi: 10.1016/s0090-4295(99)00013-8
  25. Hendin BN, Kolettis PN, Sharma RK, Thomas Jr AJ, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. Journal of Urology. 1999; 161(6): 1831-1834.
  26. Fuse H, Akashi T, Fujishiro Y, Kazama T, Katayama T. Effect of varicocele on fertility potential: comparison between impregnating and non-impregnating groups. Archives of Andrology. 1995; 35(2): 143-148. doi: 10.3109/01485019508987865
  27. Çeribas, AO, Sakin F, Türk G, Sönmez M, Ateşşahin A. Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages. Experimental and Toxicologic Pathology. 2012; 64(7-8): 717-724. doi: 10.1016/j.etp.2011.01.006
  28. Razi M, Sadrkhanloo R-A, Malekinejad H, Sarafzadeh-Rezaei F. Varicocele time-dependently affects DNA integrity of sperm cells: evidence for lower in vitro fertilization rate in varicocele-positive rats. International Journal of Fertility and Sterility. 2011; 5(3): 174-185.
  29. Zini A, De Lamirande E, Gagnon C. Low levels of nitric oxide promote human sperm capacitation in vitro. Journal of Andrology. 1996; 16(5): 424-431.
  30. Gil-Guzman E, Ollero M, Lopez MC, Sharma RK, Alvarez JG, Thomas Jr AJ, Agarwal A. Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Human Reproduction. 2001; 16(9): 1922-1930. doi: 10.1093/humrep/16.9.1922
  31. Amin M, Razi M, Sarrafzadeh-Rezaei F, Jalali AS, Najafi G. Berberine inhibits experimental varicocele-induced cell cycle arrest via regulating cyclin D1, cdk4 and p21 proteins expression in rat testicles. Andrologia. 2018; 50(4): e12984. doi: 10.1111/and.12984
  32. Duru NK, Morshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertility and Sterility. 2000; 74(6): 1200-1207. doi: 10.1016/s0015-0282(00)01591-0
  33. Bianchi PG, Manicardi GC, Bizzaro D, Bianchi U, Sakkas D. Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biology of Reproduction. 1993; 49(5): 1083-1088. doi: 10.1095/biolreprod49.5.1083
  34. Girish C, Shweta O, Raj V, Balakrishnan S, G'boy Varghese R. Ellagic acid modulates sodium valproate induced reproductive toxicity in male Wistar rats. Indian Journal of Physiology and Pharmacology. 2014; 58(4): 416-422.
  35. Bucak MN, Bodu M, Başpınar N, Güngör Ş, İli P, Acibaeva B, Topraggaleh TR, Dursun Ş. Influence of ellagic acid and Ebselen on sperm and oxidative stress parameters during liquid preservation of ram semen. Cell Journal. 2019; 12(1): 7-13. doi: 10.22074/cellj.2019.5593
  36. Han DH, Lee MJ, Kim JH. Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Research. 2006; 26(5A): 3601-3606.
Iranian Journal of Veterinary Surgery
Volume 20, Issue 2 - Serial Number 43
October 2025
Pages 137-143

  • Receive Date 19 October 2024
  • Revise Date 21 December 2024
  • Accept Date 31 December 2024
  • First Publish Date 31 December 2024