Document Type : Original Article


1 MSC Student of Developmental Biology, Department of Basic Science, Faculty of Veterinary Medicine, Ardakan University, Ardakan, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Ardakan University, Ardakan, Iran

3 Phd Graduate of Histology, Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

4 Department of Animal Sciences, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran


Cyclophosphamide leaves an undesirable effect on testes. This study was conducted to explore the effects of the Phoenix dactylifera (DP) on testes following the cyclophosphamide treatment. Thirty-six male mice were divided into six groups, one control, one cyclophosphamide, two groups of cyclophosphamide with a dose of 200 mg kg-1 and a dose of 400 mg kg-1 DP, and two of only high and low doses of DP. All groups were gavaged daily for 28 days. The animals were euthanized 24 hr after implementing the last treatment. Then, the testes and epididymis samples were removed and weighed. The main sperm characteristics such as the number of sperm and sperm viability, the morphometric changes, biochemical analysis of testes and enzyme activity were investigated. With the cyclophosphamide group, only body weight, testes weight, epididymis weight, sperm viability and the fertilization percentage were decreased significantly compared to the control group. Moreover, the spermatogenesis indices and morphometric parameters in this group indicated a significant decrease. Furthermore, the morphological changes were observed in the testicular tissue, including seminiferous tubule atrophy, vacuolation, hyperemia of blood vessels and increased space in the interstitial tissue. In the biochemical study of cyclophosphamide group, the amount of glutathione peroxidase in serum was decreased, whereas, the amount of malondialdehyde in testicular tissue showed a significant increase. The DP group included the antioxidant and anti-apoptotic properties. It seemed that the compounds in the DP would lead to the inhibition of the production of active metabolites released from the cyclophosphamide.


  1. Koff JL, Ramachandiran S, Bernal-Mizrachi L. A time to kill: targeting apoptosis in cancer. Int J Mol Sci 2015; 16(2): 2942-2955.
  2. Mohammadi F, Nikzad H, Taghizadeh M, et al. Effect of pumpkin extract regimen on testicular structure and serum biochemical parameters in cyclophosphamide-treated adult rats. KAUMS Journal (FEYZ) 2013; 17(5): 438-446.
  3. Zhou R, Wu J, Liu B, et al. The roles and mechanisms of Leydig cells and myoid cells in regulating spermato-genesis. Cell Mol Life Sci 2019; 76(4): 2681-2695.
  4. Panner Selvam MK, Agarwal A, Pushparaj PN, et al. Sperm proteome analysis and identification of fertility-associated biomarkers in unexplained male infertility. Genes (Basel) 2019; 10(7): 522. doi:10.3390/genes10070522.
  5. Hamzeh M, Hosseinimehr SJ, Karimpour A, et al. Cerium oxide nanoparticles protect cyclophosphamide-induced testicular toxicity in mice. Int J Prev Med 2019; 10: 5. doi: 10.4103/ijpvm.IJPVM_184_18.
  6. Jashni HK, Jahromi HK. Effects of palm pollen on folliculogenesis process after treatment with cyclophosphamide among rats. J Fundam Appl Sci 2016; 8(4): 1998-2007.
  7. 7Jalali AS, Hasanzadeh S, Malekinejad H. Chemo-protective effect of Crataegus monogyna aqueous extract against cyclophosphamide-induced reproductive Vet Res Forum 2011; 2(4): 266-273.
  8. Afkhami-Ardakani M, Hasanzadeh S, Shahrooz R, et al. Antioxidant effects of Spirulina platensis (Arthrospira platensis) on cyclophosphamide-induced testicular injury in rats. Vet Res Forum 2018; 9(1): 35-41.
  9. Abd El Tawab AM, Shahin NN, AbdelMohsen MM. Protective effect of Satureja Montana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact 2014; 224: 196-205.
  10. Moshfegh F, Baharara J, Namvar F, et al. Effects of date palm pollen on fertility and development of reproductive system in female Balb/C mice. J Herbmed Pharmacol 2016; 5: 23-28.
  11. Abedi A, Karimian SM, Parviz M, et al. Effect of aqueous extract of Phoenix dactylifera pollen on dopamine system of nucleus accumbens in male rats. Neurosci Med 2014; 5(1): 49-59.
  12. Selvakumar E, Prahalathan C, Mythili Y, et al. Protective effect of dl-alpha-lipoic acid in cyclophosphamide induced oxidative injury in rat testis. Reprod Toxicol 2004; 19(2): 163-167.‏
  13. Patra K, Bose S, Sarkar S, et al. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid. Chem Biol Interact 2012; 195(3): 231-239.
  14. Abedi A, Parviz M, Karamian SM, et al. Aphrodisiac activity of aqueous extract of Phoenix dactylifera pollen in male rats. Adv Sex Med 2013;3: 28-34.
  15. Biglari F, AlKarkhi AFM, Easa AM. Antioxidant activity and phenolic content of various date palm (Phoenix dactylifera) fruits from Iran. Food Chem 2008; 107(4): 1636-1641.
  16. Pedersen HS, Liu Y, Foldager L, et al. Calibration of sperm concentration for in vitro fertilization in a mouse reprotoxicity model. Toxicol In Vitro 2019; 55: 58-61.
  17. Aponte PM, van Bragt MP, de Rooij DG, et al. Spermato-gonial stem cells: characteristics and experimental possibilities. APMIS 2005; 113(11-12): 727-742.
  18. Kaya C, Barbaros Baseskioglu A, Yigitaslan S, et al. The therapeutic potential of amifostine on cyclophosphamide-induced testicular dysfunction in rats: An experimental study. Int J Reprod Biomed 2019; 17(4): 245-252.
  19. Arbabian M, Amirzadegan M, Tavalaee M, et al. Oxidative stress and its effects on male infertility: a review study. J Rafsanjan Univ Med Sci 2018; 17(3): 253-274.
  20. Aladaileh SH, Abukhalil MH, Saghir SAM, et al. Galangin activates Nrf2 signaling and attenuates oxidative damage, inflammation, and apoptosis in a rat model of cyclophosphamide-induced hepatotoxicity. Biomolecules 2019; 9(8):346. doi: 10.3390/biom9080346.
  21. Bakhtiary Z, Shahrooz R, Ahmadi A, et al. Protective effect of ethyl pyruvate on testicular histology and fertilization potential in cyclophosphamide treated mice. Vet Res Forum 2020; 11(1): 7-13.
  22. Mehraban Z, Ghaffari Novin M, Golmohammadi MG, et al. Protective effect of gallic acid on apoptosis of sperm and in vitro fertilization in adult male mice treated with cyclophosphamide. J Cell Biochem 2019; 120(10): 17250-17257.
  23. Wetzels GE, Nelemans P, Schouten JS, et al. Facts and fiction of poor compliance as a cause of inadequate blood pressure control: a systematic review. J Hypertens 2004; 22(10): 1849-1855.
  24. Ghobadi E, Moloudizargari M, Asghari MH, et al. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2017; 13(5): 525-536.
  25. Abarikwu SO, Otuechere CA, Ekor M, et al. Rutin ameliorates cyclophosphamide-induced reproductive toxicity in male rats. Toxicol Int 2012; 19(2): 207-214.
  26. Samie A, Sedaghat R, Baluchnejadmojarad T, et al. Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis. Life Sci 2018; 210: 132-139.
  27. Asleiranifam N, Hasanzadeh S, Sam MR, et al. The effects of hydro-alcoholic extract of Achillea millefolium on sperm parameters and apoptotic changes in cyclophosphamide treated mice [Persian]. J Mazandaran Univ Med Sci 2016; 25(133): 77-90.
  28. Ilbey YO, Ozbek E, Simsek A, et al. Potential chemo-protective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats. Fertil Steril 2009; 92(3): 1124-1132.
  29. Kazeminia SM, Kalaee SEV, Nasri S. Effect of dietary intake alcoholic extract of palm pollen (Phoenix dactylifera) on pituitary-testicular axis in male diabetic rats [Persian]. J Mazandaran Univ Med Sci 2014; 24(Supple 1): 167-175.