The Effect of Sustanon on Androgen Receptor Gene Expression, Testicular Histological and Gonadotropin Hormones Changes in Rats

Subject Areas : Journal of Animal Biology

Fatemeh Kamali Hossein Zadeh ¹ , Jina Khayat zadeh ² , Mohamad Mahdi Forghani Fard ³ , Armin Attaran Zadeh ⁴

1 - Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
2 - Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
3 - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
4 - Molecular Pathology and Cytogenetic Fellowship, Imam Reza Hospital, Milad Infertility Center, Mashhad University of Medical Sciences, Iran

Received: 2021-05-20 Accepted : 2021-08-03 Published : 2022-02-20

Keywords: Gonadotropin, Sustanon, AR, Sertoli, Leydig,

Abstract :

Sustanon is considered an oil-based injectable anabolic-androgenic steroid. It comprises four different testosterone esters. The principal androgen in the testis is testosterone which is mediated by the androgen receptor. The current study aimed to investigate AR gene expression and biochemical and histological analyses in male rats after using various dosages of Sustanon. There were four groups of male adult rats. The first group (control) received an intramuscular injection of Sustanon solution (peanut oil). The second, third, and fourth groups underwent the treatment with a weekly injection of different Sustanon dosages of 10, 20, and 30 mg/kg for 8 weeks, respectively. The blood samples were obtained and the measurement of the serum levels of FSH and LH were conducted. The testes were extracted for histopathological and gene expression investigation. Using generated cDNA, real-time PCR was used to evaluate AR gene expression. SPSS software was used to do statistical analysis and analysis of variance on the data. Sustanon was shown to drastically lower the number of Leydig and Sertoli cells, perhaps resulting in a large drop in FSH and LH concentrations, according to the results.The expression of AR was dose-dependent and significantly increased at a dose of 10 mg / kg and decreased significantly at a dose of 30 mg / kg compared to the control group. Sustanon is distinguished by its unique structure. It induced biochemical plus histopathological damages and changed AR gene expression in adult male rats that may cause infertility.

References:

1. Adibi A., Khoshvaghti A. 2019. A comparative study on the effects of Linum usitatissimum and Rosa domascena hydro-alcoholic extracts on body weight, thyroid hormones, and lipids profiles in rats. Journal of Shahid Sadoughi University of Medical Sciences, 27(2): 1290-1301 [In Persian]


2. Albano G.D., Amico F., Cocimano G., Liberto A., Maglietta F., Esposito M., Rosi, G.L., Di Nunno N., Salerno M., Montana A. 2021. Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review. Healthcare, 9(1): 97.


3. Aquila S., Middea E., Catalano S., Marsico S., Lanzino M., Casaburi I. 2007. Human sperm express a functional androgen receptor: effects on PI3K/AKT pathway. Human Reproduction, 22(10): 2594-2605.


4. Arazi H., Rahmati S., Ghafoori H. 2017. The interaction effects of resistance training and sustanon abuse on liver antioxidant activities and serum enzymes in male rats. Interventional Medicine and Applied Science, 9(3): 178-183.


5. Cadwallader A.B., Lim C.S., Rollins D.E., Botrè F. 2011. The androgen receptor and its use in biological assays: looking toward effect-based testing and its applications. Journal of Analytical Toxicology, 35(9): 594-607


6. Chang C., Chen Y.T., Yeh S.D., Xu Q., Wang R.S., Guillou F. 2004. Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proceedings of the National Academy of Sciences, 101(18): 6876-6881.


7. Dimitriadis F., Tsiampali C., Chaliasos N., Tsounapi P., Takenaka A., Sofikitis N. 2015. The Sertoli cell as the orchestra conductor of spermatogenesis: spermatogenic cells dance to the tune of testosterone. Hormones, 14(4): 479-503.


8. El-hanbuli H.M., Abo-Sief A.F., Mostafa T. 2017. Protective effect of silymarin on the testes of rats treated with anabolic androgenic steroid: A biochemical, histological, histochemical and immunohistochemical study. Journal of Histology and Histopathology, 4(1):10


9. García-Manso J.M., Esteve T.V. 2010. Consequences of the Use of Anabolic-Androgenic Steroids for Male Athletes’ Fertility. Springer Science+Business Media New York, 2016: 153–165.


10. Gottlieb B., Lombroso R., Beitel L.K., Trifiro M.A. 2005. Molecular pathology of the androgen receptor in male (in) fertility. Reproductive Biomedicine Online, 10(1): 42-48.


11. Gustavo M.E., da Rosa L.,  da Silveira E.L. 2014. Mechanisms of hormonal regulation of sertoli cell development and proliferation: a key process for spermatogenesis. Current Molecular Pharmacology, 7(2): 96-108.


12. Handelsman D.J. 2021. Androgen Misuse and Abuse. Endocrine Review, 42(4): 457-501


13. Holdcraft R.W., Braun R.E. 2004. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development, 131(2): 459-467.


14. Jannatifar R., Shokri S., Farrokhi A., Nejatbakhsh R. 2015. Effect of supraphysiological dose of Nandrolone Decanoate on the testis and testosterone concentration in mature and immature male rats: A time course study. International Journal of Reproductive BioMedicine, 13(12): 779-867.


15. Jan S.Z., Vormer T.L., Jongejan A., Roling M.D., Silber S.J., de Rooij D.G. 2017. Unraveling transcriptome dynamics in human spermatogenesis. Development, 144(20): 3659-3673.


16. Jan T., Jurášek M., Huml L., Rimpelová S. 2021. Medicinal Use of Testosterone and Related Steroids Revisited. Molecules, 26(4): 1032.


17. Khanlarkhani N., Pasbakhsh P., Mortezaee K., Naji M., Amidi F., Najafi A. 2016. Effect of human recombinant granulocyte colony-stimulating factor on rat busulfan-induced testis injury. Journal of Molecular Histology, 47(1): 59-67.


18. kheradmand A. 2014. Improvement of Sperm Evaluation Parameters Following Ghrelin Treatment in Cadmium-Induced Testicular Injury in Rats. Isfahan Journal of Medical Sciences, 265(31). [In Persian]


19. Lucio R.A., Tlachi-Lopez J.L., Eguibar J.R., Agmo A. 2013. Sperm count and sperm motility decrease in old rats. Physiology & Behavior, 110-111:73-79.


20. Melo C, Danin A, Silva D, Tacon J, Moura K, Costa E, et al.2010. Association between male infertility and androgen receptor mutations in Brazilian patients. Genetic and Molecular Research, 9(1): 128-133.


21. Mills NC. Androgen effects on Sertoli cells. 1990. International Journal of Andrology, 13(2):123-34.


22. Mutalip S.S.M., Shah A.M., Mohamad M., Mani V., Hussin S.N., Singh G.K.S. 2018. Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome. Journal of Basic and Clinical Physiology and Pharmacology, 30(1): 29-36.


23. Naraghi M., Abolhasani F., Kashani I., Anarkooli I., Hemadi M., Azami A. 2010. The effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the testis in adult male rats: a transmission electron microscope study. Folia Morphologica, 69(3): 138-146.


24. Purkayastha S., Mahanta R. 2012. Effect of NandroloneDecanoate on Serum FSH, LH and Testosterone Concentration in Male Albino Mice. World Journal of Life Sciences and Medical Research, 2:123-7.


25. Shahraki M.R., Mirshekari H., Shahraki A.R. 2015. Chronic Administration of High Doses of Nandrolone Decanoate on the Pituitary-Gonadal Axis in Male Rats. International Journal of High Risk Behaviors and Addiction, 4(3): 1-3


26. Shokri S., Aitken R.J., Abdolvahhabi M., Abolhasani F., Ghasemi F.M., Kashani I. 2009. Exercise and Supraphysiological Dose of Nandrolone Deconoate Increase Apoptosis in Spermatogenic Cells. Basic & Clinical Pharmacology and Toxicology, 106(4): 324-330.


27. Tahtamouni L.H., Mustafa N.H., Hassan I.M. Nandrolone decanoate administration to male rats induces oxidative stress, seminiferous tubules abnormalities, and sperm DNA fragmentation. Jordan Journal of Biological Sciences, 147(616): 1-20.


28. Tang H., Chen Y., Wang L., Yin Y., Li G., Guo Y., 2018. Fertility impairment with defective spermatogenesis and steroidogenesis in male zebrafish lacking androgen receptor. Biology and Reproduction, 98(2): 227-238.


29. Winters S.J., Moore J.P., Clark B.J. 2018. Leydig cell insufficiency in hypospermatogenesis: a paracrine effect of activin-inhibin signaling? Andrology, 6(2): 262-271.


30. Yong E.L. 2003. Androgen receptor gene and male infertility. Human Reproduction Update, 9(1): 1-7.


31. Zhou X. 2009. Roles of Androgen Receptor in Male and Female Reproduction: Lessons From Global and Cell-Specific Androgen Receptor Knockout (ARKO) Mice. Journal of Andrology, 31(3): 235-243.