Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

The Protective Effects of Exogenous Melatonin on Nicotine-induced Changes in Mouse Ovarian Follicles

Authors
1 Cellular and Molecular Research Center, Guilan University of Medical Sciences, Rasht, Iran
2 Student Research Committee, Guilan University of Medical Sciences, Rasht, Iran
3 Department of Pathology, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
Abstract
Background: Nicotine exposure causes impaired fertility and ovarian dysfunction. The aim of this study was to investigate the possible protective role of melatonin, which is known as an antioxidant agent on altered ovarian functions upon nicotine exposure. Methods: A total of 32 female adult NMRI mice were divided randomly into four groups (n=8). The control group received vehicle, while group 2 received nicotine (40 μg/kg) for 15 days and group 3 melatonin (10 mg/kg) for 5 days. Group 4 received both nicotine (40μg/kg) and melatonin (10 mg/kg) for the same periods. All animals were treated intraperitoneally. After autopsy on the 16th day, histopathological and morphometrical examinations were performed and serum estradiol concentrations were measured. The data were analyzed using ANOVA and Tukey post hoc test. A value of p < 0.05 was considered significant. Results: Nicotine significantly reduced the number of pre-antral and antral follicles, as well as estradiol concentration compared to the control group (p < 0.05). However, the decrease in the number of primordial follicles was not significant in the nicotine treated group. A significant increase in the atretic follicles were observed in group 2 compared to the control group (p < 0.05). Moreover, melatonin caused a marked normalization in the number of ovarian follicles and estradiol levels in group 4 compared to group 2. Conclusion: The results from this study suggest that melatonin may have a protective effect against nicotine-induced ovarian changes on the number of different stages of follicle growth.
Keywords

  1. Sanders SR, Cuneo SP, Turzillo AM. Effects of nicotine and cotinine on bovine theca interna and granulosa cells. Reprod Toxicol. 2002;16(6):795-800.
  2. Neal MS, Hughes EG, Holloway AC, Foster WG. Sidestream smoking is equally as damaging as mainstream smoking on IVF outcomes. Hum Reprod. 2005;20(9):2531-5.
  3. Tuttle AM, Stämpfli M, Foster WG. Cigarette smoke causes follicle loss in mice ovaries at concentrations representative of human exposure. Hum Reprod. 2009;24(6):1452-9.
  4. Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57(1):79-115.
  5. Xiao D, Huang X, Yang S, Zhang L. Direct effects of nicotine on contractility of the uterine artery in pregnancy. J Pharmacol Exp Ther. 2007;322(1): 180-5.
  6. Patil SR, Ravindra, Patil SR, Londonkar R, Patil S B. Nicotine induced ovarian and uterine changes in albino mice. Indian J Physiol Pharmacol. 1998;42 (4):503-8.
  7. Zeidler R, Albermann K, Lang S. Nicotine and apoptosis. Apoptosis. 2007;12(11):1927-43.
  8. Petrik JJ, Gerstein HC, Cesta CE, Kellenberger LD, Alfaidy N, Holloway AC. Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine. Endocrine. 2009;36(2):281-90.
  9. Adriaens I, Jacquet P, Cortvrindt R, Janssen K, Smitz J. Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis. Toxicology. 2006;228(2-3):333-43.
  10. Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 2000;7(6):444-58.
  11. Sanchez-Hidalgo M, de la Lastra CA, Carrascosa-Salmoral MP, Naranjo MC, Gomez-Corvera A, Caballero B, et al. Age-related changes in melatonin synthesis in rat extrapineal tissues. Exp Gerontol. 2009;44(5):328-34.
  12. Velkov ZA, Velkov YZh, Galunska BT, Paskalev DN, Tadjer AV. Melatonin: Quantum-chemical and biochemical investigation of antioxidant activity. Eur J Med Chem. 2009;44(7):2834-9.
  13. Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother. 2006;60(3):97-108.
  14. Bordel R, Laschke MW, Menger MD, Vollmar B. Nicotine does not affect vascularization but inhibits growth of freely transplanted ovarian follicles by inducing granulosa cell apoptosis. Hum Reprod. 2006;21(3):610-7.
  15. Khajeh Jahromi S, Mohammadghasemi F, Hajizadeh Fallah H. [Evaluation of Proliferative activity of adult mouse male germ cells following administration of different doses of nicotine]. J Iran Anat Sci. 2011;9(36):229-40. Persian.
  16. Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen L D, Manchester LC, et al. Melatonin--a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994;738:419-20.
  17. Bandyopadhyay D, Biswas K, Bandyopadhyay U, Reiter RJ, Banerjee RK. Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical. J Pineal Res. 2000;29(3):143-51.
  18. Hardeland R, Reiter RJ, Poeggeler B, Tan DX. The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev. 1993;17(3):347-57.
  19. Myers M, Britt KL, Wreford NG, Ebling FJ, Kerr J B. Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 2004;127 (5):569-80.
  20. Domingues SFS, Diniz LV, Furtado SHC, Ohashi OM, Rondina D, Silva LDM. Histological study of capuchin monkey (Cebus apella) ovarian follicles. Acta Amazon. 2004;34(3):495-501.
  21. Dorostghoal M, Khaksari Mahabadi M, Adham S. Effects of maternal caffeine consumption on ovarian follicle development in wistar rats offspring. J Reprod Infertil. 2011;12(1):15-22.
  22. Holloway AC, Kellenberger LD, Petrik JJ. Fetal and neonatal exposure to nicotine disrupts ovarian function and fertility in adult female rats. Endocrine. 2006;30(2):213-6.
  23. Kim KH, Joo KJ, Park HJ, Kwon CH, Jang MH, Kim CJ. Nicotine induces apoptosis in TM3 mouse Leydig cells. Fertil Steril. 2005;83 Suppl 1:1093-9.
  24. Holloway AC, Cuu DQ, Morrison KM, Gerstein HC, Tarnopolsky MA. Transgenerational effects of fetal and neonatal exposure to nicotine. Endocrine. 2007;31(3):254-9.
  25. Holloway AC, Petrik JJ, Bruin JE, Gerstein HC. Rosiglitazone prevents diabetes by increasing betacell mass in an animal model of type 2 diabetes characterized by reduced beta-cell mass at birth. Diabetes Obes Metab. 2008;10(9):763-71.
  26. Demiralay R, Gürsan N, Erdem H. Regulation of nicotine-induced apoptosis of pulmonary artery endothelial cells by treatment of N-acetylcysteine and vitamin E. Hum Exp Toxicol. 2007;26(7):595-602.
  27. Machaalani R, Waters KA, Tinworth KD. Effects of postnatal nicotine exposure on apoptotic markers in the developing piglet brain. Neuroscience. 2005;132(2):325-33.
  28. Jang MH, Shin MC, Jung SB, Lee TH, Bahn GH, Kwon YK, et al. Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus. Neuroreport. 2002;13(12):1509-13.
  29. Blackburn CW, Peterson CA, Hales HA, Carrell D T, Jones KP, Urry RL, et al. Nicotine, but not cotinine, has a direct toxic effect on ovarian function in the immature gonadotropin-stimulated rat. Reprod Toxicol. 1994;8(4):325-31.
  30. Gocze PM, Szabo I, Freeman DA. Influence of nicotine, cotinine, anabasine and cigarette smoke extract on human granulosa cell progesterone and estradiol synthesis. Gynecol Endocrinol. 1999;13 (4):266-72.
  31. Bódis J, Hanf V, Török A, Tinneberg HR, Borsay P, Szabó I. Influence of nicotine on progesterone and estradiol production of cultured human granulosa cells. Early Pregnancy. 1997;3(1):34-7.
  32. Barbieri RL, McShane PM, Ryan KJ. Constituents of cigarette smoke inhibit human granulosa cell aromatase. Fertil Steril. 1986;46(2):232-6.
  33. Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas CR Jr. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys. 2004;59(3): 639-53.
  34. Woo MM, Tai CJ, Kang SK, Nathwani PS, Pang S F, Leung PC. Direct action of melatonin in human granulosa-luteal cells. J Clin Endocrinol Metab. 2001;86(10):4789-97.
  35. Kim JK, Lee CJ. Effect of exogenous melatonin on the ovarian follicles in gamma-irradiated mouse. Mutat Res. 2000;449(1-2):33-9.
  36. Cagnacci A, Soldani R, Yen SS. Exogenous melatonin enhances luteinizing hormone levels of women in the follicular but not in the luteal menstrual phase. Fertil Steril. 1995;63(5):996-9.
  37. Bódis J, Koppán M, Kornya L, Tinneberg HR, Török A. Influence of melatonin on basal and gonadotropin-stimulated progesterone and estradiol secretion of cultured human granulosa cells and in the superfused granulosa cell system. Gynecol Obstet Invest. 2001;52(3):198-202.
  38. Webley GE, Leidenberger F. The circadian pattern of melatonin and its positive relationship with progesterone in women. J Clin Endocrinol Metab. 1986;63(2):323-8.
  39. Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, et al. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril. 2009;92(1):328-43.
  40. Mohamad Ghasemi F, Faghani M, Khajeh Jahromi S, Bahadori M, Nasiri E, Hemadi M. Effect Of Melatonin On Pproliferative Activity And Apoptosis In Spermatogenic Cells In Mouse Under Chemotherapy. J Reprod Contracept. 2010; 21(2):79–94.
  41. Hill SM, Blask DE. Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res. 1988;48(21):6121-6.
  42. Lissoni P, Barni S, Meregalli S, Fossati V, Cazzaniga M, Esposti D, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer. 1995;71(4):854-6.