Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Effects of Tamoxifen on DNA Integrity in Mice

Authors
1 Department of Biology and Anatomical Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
Background: Tamoxifen (TX) is widely used to treat idiopathic infertility in men. Using TX has been shown to produce sperm in patients with oligospermia and azoospermia and improve male fertility. The aim of this study was to evaluate the effects of TX on DNA and chromatin quality in mice regarding the importance of chromatin quality and sperm DNA at all stages of reproduction. Methods: 24 male NMRI mice were divided into 3 groups including dose 0.4 mg/kg/day that received basal diet and TX, dose 0.6 mg/kg/day that received basal diet and TX, and group 3 that received vehicle for 35 days as the control. After that, epididymal spermatozoa were analyzed for nuclear DNA quality. One-way ANOVA was performed with a Tukey test to compare sperm DNA fragmentation at different times. The p<0.05 was considered significant. Results: The use of different doses of TX may have detrimental effects on sperm chromatin protamination and DNA integrity in mice. According to Acridine Orange (AO) staining, the rate of increased single-stranded DNA damage was observed at 0/6 mg/kg/day TX dose (p<0.05). Conclusion: The use of different studied TX doses in the animal sample was found to increase the amount of protamine deficiency and DNA defect in treated mice.
Keywords

  1. Xu ZP, Sun HX, Zhang NY. [Sperm DNA damage and assisted reproductive technology]. Zhonghua Nan Ke Xue. 2008;14(3):259-63. Chinese.
  2. Talebi AR, Sarcheshmeh AA, Khalili MA, Tabibnejad N. Effects of ethanol consumption on chromatin condensation and DNA integrity of epididymal spermatozoa in rat. Alcohol. 2011;45(4):403-9.
  3. AinMelk Y, Belisle S, Carmel M, Jean-Pierre T. Tamoxifen citrate therapy in male infertility. Fertil Steril. 1987;48(1):113-7.
  4. Traub A, Thompson W. The effect of tamoxifen on spermatogenesis in subfertile men. Andrologia. 1981;13(5):486-90.
  5. Moein MR, Tabibnejad N, Ghasemzadeh J. Beneficial effect of tamoxifen on sperm recovery in infertile men with nonobstructive azoospermia. Andrologia. 2012;44 Suppl 1:194-8.
  6. Patankar SS, Kaore SB, Sawaneh MV, Mishra NV, Deshkari AM. Short communication effect of clomiphene citrate on sperm density in male partners of infertile couples. Indian J Physiol Pharmacol. 2007;51(2):195-8.
  7. Ko SC, Kim DG, Han CH, Lee YJ, Lee JK, Byun HG, et al. Nitric oxide-mediated vasorelaxation effects of anti-angiotensin I-converting enzyme (ACE) peptide from Styela clava flesh tissue and its anti-hypertensive effect in spontaneously hypertensive rats. Food Chem. 2012;134(2):1141-5.
  8. Richthoff J, Spano M, Giwercman YL, Frohm B, Jepson K, Malm J, et al. The impact of testicular and accessory sex gland function on sperm chromatin integrity as assessed by the sperm chromatin structure assay (SCSA). Hum Reprod. 2002;17(12):3162-9.
  9. Oosterhuis GJ, Mulder AB, Kalsbeek-Batenburg E, Lambalk CB, Schoemaker J, Vermes I. Measuring apoptosis in human spermatozoa: a biological assay for semen quality? Fertil Steril. 2000;74(2):245-50.
  10. Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993;75(6):1169-78.
  11. Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001;22(4):604-10.
  12. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003;9(4):331-45.
  13. Virant-Klun I, Tomazevic T, Meden-Vrtovec H. Sperm single-stranded DNA, detected by acridine orange staining, reduces fertilization and quality of ICSI-derived embryos. J Assist Reprod Genet. 2002;19(7):319-28.
  14. Talebi A, Moein M, Tabibnejad N, Ghasemzadeh J. Effect of varicocele on chromatin condensation and DNA integrity of ejaculated spermatozoa using cytochemical tests. Andrologia. 2008;40(4):245-51.
  15. Kazerooni T, Asadi N, Jadid L, Kazerooni M, Ghanadi A, Ghaffarpasand F, et al. Evaluation of sperm's chromatin quality with acridine orange test, chromomycin A3 and aniline blue staining in couples with unexplained recurrent abortion. J Assist Reprod Genet. 2009;26(11-12):591-6.
  16. Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC, Thomas AJ Jr. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril. 2003;80(6):1431-6.
  17. Talebi A, Vahidi S, Aflatoonian A, Ghasemi N, Ghasemzadeh J, Firoozabadi R, et al. Cytochemical evaluation of sperm chromatin and DNA integrity in couples with unexplained recurrent spontaneous abortions. Andrologia. 2012;44 Suppl 1:462-70.
  18. Simões R, Feitosa WB, Mendes CM, Marques MG, Nicacio AC, de Barros FR, et al. Use of chromomycin A3 staining in bovine sperm cells for detection of protamine deficiency. Biotech Histochem. 2009;84(3):79-83.
  19. Nasr-Esfahani MH, Razavi S, Mardani M. Relation between different human sperm nuclear maturity tests and in vitro fertilization. J Assist Reprod Genet. 2001;18(4):219-25.
  20. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Human Reproduction. 2003;9(4):331-45.
  21. Ramezani M, Khalili MA, Adib M. Effect of vitrification on apoptosis and some of parameter of sperm in infertile men. Feyz. 2010;14(1):18-25.
  22. Duran EH, Morshidi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod. 2002;17(12):3122-8.
  23. Nasr-Esfahani MH, Razavi Sh, Moradi M. Relation between different human sperm nuclear maturity tests & in vitro fertilization. J Assist Reprod Genet. 2001;18(4):219-25.
  24. Dehghani Ashkezari M, Kalantar SM, Parivar K, Aflatoonian A. The correlation between sperm DNA integrity and IVF success rate in infertile couples. J Reprod Infertil. 2006;6(5):505-12.
  25. Oryan Sh, Parivar K, Asle rousta M. Effect of tamoxifen on histological structure of testis in adult male Wistar rats. Med Sci J Islam Azad Univ Tehran Med Branch. 2008;18(2):81-4.
  26. Motrich RD, Ponce AA, Rivero VE. Effect of tamoxifen treatment on the semen quality and fertility of the male rat. Fertil Steril. 2007;88(2):452-61.
  27. Nada EA, El Taieb M, Ibrahim HM, Al Saied AE. Efficacy of tamoxifen and l‐carnitine on sperm ultrastructure and seminal oxidative stress in patients with idiopathic oligoasthenoteratozoospermia. Andrologia. 2015;47(7):801-10.
  28. Chua M, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta‐analysis. Andrology. 2013;1(5):749-57.
  29. Pathak S, Kedia-Mokashi N, Saxena M, D'Souza R, Maitra A, Parte P, et al. Effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 locus-specific DNA methylation in rat spermatozoa and its association with embryo loss. Fertil Steril. 2009;91(5 Suppl):2253-63.
  30. Oakes C, La Salle S, Smiraglia DJ, Robaire B, Trasler JM. Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells. Dev Biol. 2007;307(2):368-79.
  31. Burns JL, Hassan AB. Cell survival and proliferation are modified by insulin-like growth factor 2 between days 9 and 10 of mouse gestation. Development. 2001;128(19):3819-30.
  32. Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, et al. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007;16(21):2542-51.
  33. Marques CJ, Costa P, Vaz B, Carvalho F, Fernandes S, Barros A, et al. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod. 2008;14(2):67-74.
  34. Aleem M, Padwal V, Choudhari J, Balasinor N, Parte P, Gill‐Sharma M. Effects of tamoxifen citrate on gene expression during nuclear chromatin condensation in male rats. Asian J Androl. 2005;7(3):311-21.