Published date: Jan 09 2023

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 20, Issue No. 12

Pages: 999–1006

DOI: 10.18502/ijrm.v20i12.12560

Zeinab BahramiDepartment of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Neda DaeifarshbafDepartment of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Fatemehsadat AmjadiDepartment of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Reza AflatoonianR.Aflatoonian@gmail.comLaleh IVF Clinic, Laleh Hospital, Tehran, Iran.

Background: Hormonal imbalance is one of the important etiological factors for Oligoasthenoteratospermias (OAT).

Objective: This study aimed to evaluate the effects of hormonal changes including prolactin, TSH, testosterone, luteinizing hormone, follicle-stimulating hormone, and anti-Mullerian hormone on sperm DNA fragmentation in normal men compared with OAT to design a clinical algorithm for the comprehensive study of male factor infertilities.

Materials and Methods: We consecutively selected 60 candidates referred to the infertility clinic to collect the semen and blood samples. Then, a terminal deoxynucleotidyl transferase dUTP nick end labeling test was performed to evaluate the sperm DNA fragmentation index (DFI). After semen analysis and DFI checking, they were classified into 4 groups consisting of normospermia and OAT men each with or without increased DFI. Hormone parameters were analyzed using enzyme-linked immunoassay.

Results: Follicle-stimulating hormone and luteinizing hormone levels showed positive correlations with DFI in a significant way (p ≤ 0.01), while testosterone and thyroidstimulating hormone were associated with sperm concentration. Prolactin and anti- Mullerian hormone levels significantly correlated (p ≤ 0.01) with sperm concentration and DFI value simultaneously.

Conclusion: Decreased and increased levels of serum hormones could adversely affect semen profile and sperm DNA integrity which lead to severe male infertility. Although we investigated the effects of the main hormones related to male infertility on DNA damage, the role of these hormones on the fertilization rate and embryo quality needs to be evaluated in further studies.

Key words: DNA fragmentation, Oligospermia, Asthenospermia, Teratospermia, Hormones.

[1] Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 2015; 8: 191–196.

[2] McLachlan RI. Approach to the patient with oligozoospermia. J Clin Endocrinol Metab 2013; 98: 873–880.

[3] Azad N, Nazarian H, Ghaffari Novin M, Masteri Farahani R, Piryaei A, Heidari MH, et al. Oligoasthenoteratozoospermic (OAT) men display altered phospholipase C ζ (PLCζ) localization and a lower percentage of sperm cells expressing PLCζ and postacrosomal sheath WW domain-binding protein (PAWP). Bosn J Basic Med Sci 2018; 18: 178–184.

[4] Jimoh AAG, Olawui TS, Omotoso GO, Oyewopo AO, Dare JK. Semen parameters and hormone profile of men investigated for infertility at Midland Fertility Centre, Ilorin, Nigeria. J Basic Appl Sci 2012; 8: 110–113.

[5] Moslemi Mehni N, Ketabchi AA, Hosseini E. Combination effect of pentoxifylline and L-carnitine on idiopathic oligoasthenoteratozoospermia. Iran J Reprod Med 2014; 12: 817–824.

[6] Wosnitzer M, Goldstein M, Hardy MP. Review of azoospermia. Spermatogenesis 2014; 4: e28218.

[7] Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, et al. Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrinol 2018; 16: 87.

[8] Ribas-Maynou J, Benet J. Single and double strand sperm DNA damage: Different reproductive effects on male fertility. Genes 2019; 10: 105.

[9] Qiu Y, Yang H, Li Ch, Xu Ch. Progress in research on sperm DNA fragmentation. Med Sci Monit 2020; 26: e918746.

[10] Oduwole OO, Peltoketo H, Huhtaniemi IT. Role of follicle-stimulating hormone in spermatogenesis. Front Endocrinol 2018; 9: 763.

[11] McLachlan RI, Wreford NG, Robertson DM, de Kretser DM. Hormonal control of spermatogenesis. Trends Endocrinol Metab 1995; 6: 95–101.

[12] Xu H-Y, Zhang H-X, Xiao Zh, Qiao J, Li R. Regulation of antimüllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J Androl 2019; 21: 109–114.

[13] Grinspon RP, Rey RA. Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism. Horm Res Paediatr 2010; 73: 81–92.

[14] Ramaswamy S, Weinbauer GF. Endocrine control of spermatogenesis: Role of FSH and LH/testosterone. Spermatogenesis 2014; 4: e996025.

[15] Wdowiak A, Raczkiewicz D, Stasiak M, Bojar IJNL. Levels of FSH, LH and testosterone, and sperm DNA fragmentation. Neuro Endocrinol Lett 2014; 35: 73–79.

[16] Verdi A, Nasr-Esfahani MH, Forouzanfar M, Tavalaee M. The effect of recombinant human follicle-stimulating hormone on sperm quality, chromatin status and clinical outcomes of infertile oligozoospermic men candidate for intracytoplasmic sperm injection: A randomized clinical trial. Int J Fertil Steril 2021; 15: 1–7.

[17] Ghasemian F, Mirroshandel SA, Zahiri Z. Impact of hormonal changes on the semen quality and assisted reproductive outcomes in infertile men. J Appl Biomed 2017; 15: 227–232.

[18] Simoni M, Santi D, Negri L, Hoffmann I, Muratori M, Baldi E, et al. Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p. N680S: A pharmacogenetic study. Hum Reprod 2016; 31: 1960–1969.

[19] Bates JN, Kohn TP, Pastuszak AW. Effect of thyroid hormone derangements on sexual function in men and women. Sex Med Rev 2020; 8: 217–230.

[20] Wajner SM, Wagner MS, Maia AL. Clinical implications of altered thyroid status in male testicular function. Arq Bras Endocrinol Metabol 2009; 53: 976–982.

[21] Castaneda Cortes DC, Langlois VS, Fernandino JI. Crossover of the hypothalamic pituitary-adrenal/ interrenal, -thyroid, and -gonadal axes in testicular development. Front Endocrinol 2014; 5: 139.

[22] Singh P, Singh M, Cugati G, Singh AK. Hyperprolactinemia: An often missed cause of male infertility. J Hum Reprod Sci 2011; 4: 102–103.

[23] Gardner DK, Weissman A, Howles CM, Shoham Z. Textbook of assisted reproductive techniques. 5th Ed. USA, Florida: CRC Press; 2018.

[24] World Health Organization. Who laboratory manual for the examination and processing of human semen. 5th Ed. Switzerland: World Health Organization Press; 2010.

[25] Zandieh Z, Ashrafi M, Aflatoonian K, Aflatoonian RJA. Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube. Andrology 2019; 7: 228–234.

[26] Khourdaji I, Lee H, Smith RP. Frontiers in hormone therapy for male infertility. Transl Androl Urol 2018; 7 (Suppl.): S353–S366.

[27] Wdowiak A, Raczkiewicz D, Stasiak M, Bojar I. Levels of FSH, LH and testosterone, and sperm DNA fragmentation. Neuro Endocrinol Lett 2014; 35: 73–79.

[28] Lu J-Ch, Jing J, Chen L, Ge Y-F, Feng R-X, Liang Y-J, et al. Analysis of human sperm DNA fragmentation index (DFI) related factors: A report of 1010 subfertile men in China. Reprod Biol Endocrinol 2018; 16: 23.

[29] Colacurci N, Monti MG, Fornaro F, Izzo G, Izzo P, Trotta C, et al. Recombinant human FSH reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia. J Androl 2012; 33: 588–593.

[30] Muratori M, Baldi E. Effects of FSH on sperm DNA fragmentation: review of clinical studies and possible mechanisms of action. Front Endocrinol 2018; 9: 734.

[31] Colacurci N, de Leo V, Ruvolo G, Piomboni P, Caprio F, Pivonello R, et al. Recombinant FSH improves sperm DNA damage in male infertility: A phase II clinical trial. Front Endocrinol 2018; 9: 383.

[32] Wei T-Ch, Huang WJ, Lin ATL, Chen K-K. The role of hormones on semen parameters in patients with idiopathic or varicocele-related oligoasthenoteratozoospermia (OAT) syndrome. J Chin Med Assoc 2013; 76: 624–628.

[33] Trussell JC, Coward RM, Santoro N, Stetter Ch, Kunselman A, Diamond MP, et al. Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population. Fertil Steril 2019; 111: 1129–1134.

[34] Sharma MK, Parchwani D, Maheria P, Upadhyah A. Relationship between thyroid profile and semen quality. Natl J Commun Med 2012; 3: 20–24.

[35] Nikoobakht MR, Aloosh M, Nikoobakht N, Mehrsay A, Biniaz F, Karjalian MA. The role of hypothyroidism in male infertility and erectile dysfunction. Urol J 2012; 9: 405– 409.

[36] Ralph O, Shroff N. Prolactinoma: A rare, important and treatable cause of male infertility. J Clin Urol 2019; 14: 524– 526.

[37] Dabbous Z, Atkin SL. Hyperprolactinaemia in male infertility: Clinical case scenarios. Arab J Urol 2018; 16: 44– 52.

[38] Keskin MZ, Budak S, Gubari S, Celik O, Yalbuzdag O, Ilbey Y. The effect of hyperprolactinemia on semen parameters. J Clin Anal Med 2016; 7: 757–759.

[39] Xu H-Y, Zhang H-X, Xiao Z, Qiao J, Li R. Regulation of anti- Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J Androl 2019; 21: 109–114.

[40] Peng L-P, Shao Y, Wang C-C, Zou Z-C, Shen T, Chen L, et al. [Correlation of serum anti-müllerian hormone with semen parameters]. Zhonghua Nan Ke Xue 2017; 23: 531–535. (in Chinese).

[41] Appasamy M, Muttukrishna S, Pizzey A, Ozturk O, Groome N, Serhal P, et al. Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility. Reprod Biomed Online 2007; 14: 159– 165.