Effect of amifostine on sperm DNA fragmentation and testes after radioiodine treatment

Open access

Abstract

Introduction: Radioactive iodine (RAI) is commonly used for the treatment of hyperthyroidism caused by Graves’ disease or thyroid nodules. However, information available on the impact of RAI therapy on male gonadal function is scarce. This study aimed to determine any possible damage to testicular tissue and sperm quality caused by RAI therapy, and the radioprotective effect of amifostine against such damage.

Material and Methods: In total, 36 rats were randomly allocated to three groups, including a control group, RAI group (111 MBq Iodine-131), and RAI + amifostine group (111 MBq Iodine-131 and a single dose of 200 mg/kg amifostine). Blood and epididymal sperm samples were taken for hormone analyses and the evaluation of spermatological parameters. The TUNEL assay and haematoxylin-eosin were used to stain testicular tissue samples to detect histological changes and apoptosis.

Results: The groups differed insignificantly for the testicular mass index and spermatozoa concentration. However, spermatozoa motility and percentage of viable spermatozoa were higher in the RAI + amifostine group, compared to the RAI group. Sperm DNA fragmentation and the index of apoptotic germ cells significantly decreased in the amifostine group, in comparison to the radioiodine group. While the testosterone levels showed no significant change, the follicle stimulating hormone (FSH) levels significantly decreased in the RAI + amifostine group.

Conclusion: All histopathological parameters and some spermatological parameters showed that RAI therapy caused statistically significant damage of testicular tissue and this damage was reduced by amifostine.

References

  • 1. Bujan L., Walschaerts M., Moinard N., Hennebicq S., Saias J., Brugnon F., Auger J., Berthaut I., Szerman E., Daudin M., Rives N.: Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network. Fertil Steril 2013, doi:10.1016/j.fertnstert.2013.05.018.

  • 2. Ceccarelli C., Battisti P., Gasperi M., Fantuzzi E., Pacini F., Gualdrini G., Pierantoni M.C., Luciani A., Djokich D., Pinchera A.: Radiation dose to the testes after 131I therapy for ablation of post surgical thyroid remnants in patients with differentiated thyroid cancer. J Nucl Med 1999, 40, 1716–1721.

  • 3. Celik K.O., Aras A., Tugan D., Hekimgil M., Yalman D., Esassolak M., Haydaroglu A.: The relationship between radiation-induced apoptosis in rat germ cells and amifostine. T Klin J Med Sci 2004, 24, 142–146.

  • 4. Clouthier D.E., Averbock M.R., Maika S.D., Hammer R.E., Brinster R.L.: Rat spermatogenesis in mouse testis. Nature 1996, doi:10.1038/381418a0.

  • 5. Clyde H.R., Walsh P.C., English R.W.: Elevated plasma testosterone and gonadotropin levels in infertile males with hyperthyroidism. Fertil Steril 1976, 27, 662–666.

  • 6. Esquerré-Lamare C., Isus F., Moinard N., Bujan L.: Sperm DNA fragmentation after radioiodine treatment for differentiated thyroid cancer. Basic Clin Androl 2015, doi: 10.1186/s12610-015-0024-1.

  • 7. Etebari M., Jafarian-Dehkordi A., Lame V.: Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity. Res Pharm Sci 2005, 10, 68–74.

  • 8. Evan G., Littlewood T.: A matter of life and cell death. Science 1998, 281, 1317–1321.

  • 9. Franca L.R., Russel L.D.: The testis of domestic animals. In: Male reproduction: a multidisciplinary overview, edited by F. Martinez-Garcia, J. Regadera, Madrid, 1998, pp. 198–219.

  • 10. Gudeloglu A., Parekattil S.J.: Update in the evaluation of the azoospermic male. Clinics (Sao Paulo) 2013, 68, 27–34.

  • 11. Sen C.C., Yumusak N., Faundez R., Temamogullari., Taskin A.: Evaluation of intra-testicular injections of calcium chloride and 4-vinylcyclohexene 1,2 monoepoxide for chemical sterilization in guinea pigs. Pol J Vet Sci 2017, doi:10.1515/pjvs-2017-0030.

  • 12. Howell S.J., Shalet S.M.: Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr 2005, doi:10.1093/jncimonographs/lgi003.

  • 13. Hyer S., Vini L., O'Connell M., Pratt B., Harmer C.: Testicular dose and fertility in men following I(131) therapy for thyroid cancer. Clin Endocrinol (Oxf) 2002, 56, 755–758.

  • 14. Krassas G.E.: The male and female reproductive system in thyrotoxicosis. In: the thyroid: A fundamental and clinical text, edited by S.C. Werner, S.H. Ingbar, L.E. Braverman, R.D. Utiger, Philadelphia, 2005, pp. 621–628.

  • 15. Kuker R., Sztejnberg M., Gulec S.: I-124 imaging and dosimetry. Mol Imaging Radionucl Ther 2017, doi:10.4274/2017.26.suppl.07.

  • 16. Lassmann M., Hanscheid H., Gassen D., Biko J., Meineke V., Reiners C., Scherthan H.: In vivo formation of gamma-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer. J Nucl Med 2010, doi:10.2967/jnumed.109.071357.

  • 17. Luo D.Y., Yang G., Liu J.J., Yang Y.R, Dong Q.: Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in rat Leydig cells. Asian J Androl 2011, doi:10.1038/aja.2010.111

  • 18. Ozturk M.I, Koca K., Keles M.O., Yilmaz S., Karaman M.I.: Increased sperm DNA damage in experimental rat varicocele model and the beneficial effect of varicocelectomy. Int J Fertil Steril 2012, 6, 95–100.

  • 19. Pacini F, Gasperi M, Fugazzola L., Ceccarelli C., Lippi F., Centoni R., Martino E., Pinchera A.: Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine. J Nucl Med 1994, 35, 1418–1422.

  • 20. Robbins R.J., Schlumberger M.J.: The evolving role of (131)I for the treatment of differentiated thyroid carcinoma. J Nucl Med 2005, 46, 28–37.

  • 21. Sahintürk V., Güclü C., Baycu C.: Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats. Asian J Androl 2007, doi:10.1111/j.1745-7262.2007.00229.x.

  • 22. Sakhaee E., Abshenas J., Kheirandish R., Azari O., Mirzabeigi F., Mostafavi A.: Adverse effects of Zataria multiflora boiss on epididymal sperm quality, and testicular tissue following experimentally induced copper poisoning in mice. Basic Res J Med Clin Sci 2013, 2, 27–31.

  • 23. Si W., Benson J.D., Men H., Critser J.K.: Osmotic tolerance limits and effects of cryoprotectants on the motility, plasma membrane integrity and acrosomal integrity of rat sperm. Cryobiology 2006, doi: 10.1016/j.cryobiol.2006.09.001.

  • 24. Simon B., Lee S.J., Partridge A.H., Runowicz C.D: Preserving fertility after cancer. CA Cancer J Clin 2005, 55, 211–228.

  • 25. Sklar C.: Reproductive physiology and treatment-related loss of sex hormone production. Med Pediatr Oncol 1999, 33, 2–8.

  • 26. Vendramini V., Sasso-Cerri E., Miraglia S.M.: Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status Reprod Biol Endocrinol 2010, doi: 10.1186/1477-7827-8-3.

  • 27. Wang S.J., Jin J.H., Xu J.X., Wu Z.F., Lu K.Y., Li C.G., Lei Z.L., Li S.J: Radioiodine-131 therapy improves sex hormones and sexual function in male patients with Graves' disease. Zhonghua Nan Ke Xue 2012, 18, 542–544.

  • 28. Wichers M., Benz E., Palmeto H., Biersack H.J., Grunwald F., Klingmuller D.: Testicular function after radioiodine therapy for thyroid carcinoma. Eur J Nucl Med 2000, 27, 503–507.

  • 29. Xu G., Zhang W., Bertram P., Zheng XF., McLeod H.: Pharmacogenomic profiling of the PI3K/PTEN-AKT-mTOR pathway in common human tumors. Int J Oncol 2004, 24, 893–900.

Journal of Veterinary Research

formerly Bulletin of the Veterinary Institute in Pulawy

Journal Information


IMPACT FACTOR Bull Vet Inst Pulawy 2016: 0.462

CiteScore 2016: 0.46

SCImago Journal Rank (SJR) 2015: 0.230
Source Normalized Impact per Paper (SNIP) 2015: 0.383

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 60 60 43
PDF Downloads 19 19 16