Administration of melatonin protects against acetylsalicylic acid-induced impairment of male reproductive function in mice

Document Type: Original Article


1 Student Research Center, Guilan University of Medical Sciences, Rasht-Iran

2 Anatomy Department, Faculty of Medicine, Guilan University of Medical Sciences, Rasht-Iran

3 Cellular & Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht-Iran


Objective(s): Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA).
Materials and Methods: Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA.
Results: Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters (P<0.05), as well as a decrease in the integrity of sperm chromatin (P<0.01). ASA treatment also reduced serum testosterone and TAC levels (P<0.05). Co-administration of melatonin with ASA significantly improved epididymal sperm parameters and increased serum testosterone and TAC levels compared to the ASA-treated group. LH level was not different in the combined treatment group compared to control or ASA treatment.
Conclusion: Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone.


Main Subjects

1. Wiweko B, Utami P. Predictive value of sperm deoxyribonucleic acid (DNA) fragmentation index in male infertility. Basic Clin Androl 2017; 27:1-7.

2.Fortan P, Hawkey C. Drug-induced gastrointestinal disorders. Medicine 2007; 35:210-215.

3.Gupta C, Gentlejewski C. Role of prostaglandins in the testosterone dependent wolffian duct differentiation of the fetal mouse. Biol Reprod 1992; 47:1151-1160.

4.Balaji T, Ramanathan M, Menon V. Localization of cyclooxygenase-2 in mice vas deferens and its effects on fertility upon suppression using nimesulide: a preferential cyclooxygenase-2 inhibitor. Toxicol 2007; 234:135-144.

5.Gottlieb C, Svanborg K, Eneroth P, Bygdeman M. Effect of prostaglandins on human sperm function in vitro and seminal adenosine triphosphate content. Fertil Steril 1988; 49:322-327.

6.Kennedy J, Korn N, Thurston R. Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility. Reprod Biol Endocrinol 2003; 1:74.

7.Tripiciano A, Filippini A, Ballarini F, Palombi F. Contractile response of peritubularmyoid cells to prostaglandin F2alpha. Mol Cell Endocrinol 1998; 138:143-150.

8.Qstensen M, Khamashta M, Lokshin M, Parke A, Brucato A, Carp H, et al. Anti- inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther 2006; 8:209.

9.Martínez M, Greenberg E. More aspirin for less cancer?. J Natl Cancer Inst  2007; 99:582-583.

10.Didolkar A, Patel P, Roychowdhury D. Effect of aspirin on spermatogenesis in mature and immature rats. Int J Androl 1980; 3:585-593.

11.Didolkar A, Gurjar A, Joshi U, Sheth A, Roychowdhury D. Effects of aspirin on blood plasma levels of testosterone, LH and FSH in maturing male rats. Int J Androl 1980; 3:312-318.

12.Gwayi N, Bernard R. The effects of melatonin on sperm motility in vitro in Wistar rats. Andrologia 2002; 34:391-396.

13.Hemadi M, Saki G, Shokri S, Ghasemi F. Follicular dynamics in neonate vitrified ovarian grafts after host treatment with melatonin. Folia Morphol  2011; 70:18-23.

14.Stutz G, Zamudio J, Santillán M, Vincenti L, de Cuneo M, Ruiz R. The effect of alcohol, tobacco, and aspirin consumption on seminal quality among healthy young men. Arch Environ Health 2004; 59:548-552.

15.Polat A, Emre M. Influence of melatonin and acetylsalicylic acid on lipid peroxidation and antioxidant enzyme activities in gastric mucosa. J Gastroenterol 2006; 41:507-508.

16.Hussein M, Abu-Dief E, Abou El-Ghait A, Adly M, Abdelraheem M. Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats: an animal model. Int J Exp Pathol 2006; 87:237-250.

17.Reiter R, Tan D, Manchester L, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys  2001; 34:237-256.

18.Altintas R, Polat A, Parlakpinar H, Vardi N, Beytur A, Oguz F, et al. The effect of melatonin on acetylsalicylic acid-induced kidney and testis damage. Hum Exp Toxicol 2014; 33:383-395.

19.World Health Organisation. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. Geneva: WHO. 2010; 7-37.

20.Shokri S, Aitken R, Abdolvahhabi M, Abolhasani F, Ghasemi F, Kashani I, et al. Exercise and supraphysiological dose of nandrolonedecanoate increase apoptosis in spermatogenic cells. Basic Clin Pharmacol Toxicol 2010; 106:324-330.

21.Fakoya F, Caxton-Martins E. Morphological alterations in the seminiferous tubules of adult Wistar rats: the effects of prenatal ethanol exposure.  Folia Morphol  2004; 63: 195-202.

22.Aral F, Karaçal F, Baba F. The effect of enrofloxacin on sperm quality in male mice. Res Vet Sci  2008; 84:95-99.

23.Mohamadghasemi F, Faghani M, Jahromi SK, Bahadori M, Nasiri E, Hemadi M. Effect of Melatonin on proliferative activity and apoptosis in spermatogenic cells in mouse under chemotherapy. J Reprod Contracept 2010; 21:79-94.

24.Dare W, Noronha C, Kusemiju O, Okanlawon O. The effect of ethanol on spermatogenesis and fertility in male Sprague-Dawley rats pretreated with acetylsalicylic acid Niger. Postgrad Med J 2002; 9:194-198.

25.Vyas A, Ram H, Purohit A, Jatwa R. Adverse Effects of Subchronic Dose of Aspirin on Reproductive Profile of Male Rats. J Pharm  2016; 6585430.

26.Oyedeji K, Bolarinwa A, Adigun A. Effect of aspirin on reproductive functions in male albino rats.  Res J Pharm  2013; 7: 16-20.

27.Vane J, Botting R. The mechanism of action of aspirin. Trombosis Res  2003; 110:255-258.

28.Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother  2006; 60:97-108.

29.Shang X, Huang Y, Ye Z, Yu X, Gu W. Protection of melatonin against damage of sperm mitochondrial function induced by reactive oxygen species. Zhonghua Nan KeXue 2004; 10:604-607.

30.Kokolis N, Theodosiadou E, Tsantarliotou M, Rekkas C, Goulas P, Smokovitis A. The effect of melatonin implants on blood testosterone and acrosin activity in spermatozoa of the ram. Andrologia 2000; 32:107-114.

31.Roodbari F, Abedi N, TalebiAR. Early and late effects of Ibuprofen on mouse sperm parameters, chromatin condensation, and DNA integrity in mice. Iran J Reprod Med. 2015; 13:703-710.

32.Shefi S, Turek P. Definition and current evaluation of subfertile men. Int Braz J Urol  2006; 32:385-397.

33.Evenson D. The sperm chromatin structure assay (SCSA) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim Reprod Sci  2016; 169:56-75.

34.Tanyildizi S, Bozkurt T. Effects of acetylsalicylic acid and metamizol on hyaluronidase activity and sperm characteristics in rams. Anim Reprod Sci 2003; 76:195-204.

35.Asok K, Chinoy N. Effects of acetylsalicylic acid on reproductive organs of adolescent male rats. Endocrinol Exp  1988; 22:187-195.

36.Ateşşahin A, Sahna E, Türk G, Ceribaşi AO, Yilmaz S, Yüce A, et al. Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res  2006; 41:21-27.

37.Mohammadghasemi F, Jahromi SK, Hajizadeh H, Homafar MA, Saadat S. The Protective Effects of Exogenous Melatonin on nicotine-induced changes in mouse ovarian follicles. J Reprod Infertil 2012; 13:143-150.

38.Saadat S, Mohammadghasemi F, Jahromi SK, Homafar M, Haghiri M. Melatonin protects uterus and oviduct exposed to nicotine in mice. Interdiscip Toxicol 2014; 7:41-46.

39.Brzozowski T, Konturek P, Zwirska-Korczala K, Konturek S, Brzozowska I, Drozdowicz D, et al. Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress-induced damage. J Pineal Res. 2005; 39:375-385.