Effects of L-Arginine and L-Nitro-Arginine Methyl Ester (L-NAME) in the First Half of Pregnancy on Embryos and Offspring Testis Tissue Before and After Birth

Document Type : Original Article (s)

Authors

1 Department of Animal Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran

2 Professor, Department of Animal Biology, School of Biological Sciences, Kharazmi University, Tehran, Iran

3 Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Research Instructor, Isfahan Neurosciences Research Center, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Considering nitric oxide (NO) as one of the important molecular regulators in genital organs, and according to the critical level of it in establishing a successful pregnancy, we assessed the changes in testis tissue of embryo and offspring via treating pregnant mice.Methods: 35 adult female mice, after observing the vaginal plug, were randomly divided into five groups of seven. The first one was the control group. Remaining groups, respectively, received L-Arginin, L-nitro-arginine methyl ester (L-NAME), normal saline, and a mixture of L-Arginin and L–NAME, three days in first half of pregnancy. One day before the delivery, and before maturation, embryos’ and offspring’s testes were removed through laparotomy. Pathological and histological changes of samples were assessed using histotechnique method and general Hematoxylin and Eosin (H&E) staining.Findings: In L-NAME group, in addition to disorganization in tissue order, tunica albuginea diameter was considerably increased whereas the number of germ cells was significantly decreased in embryos and offspring. L. Arginine treatment in pregnant mice led to reduce the number of seminiferous tubules and decrease tunica albuginea diameter and dissemination.Conclusion: Stimulating or inhibiting the synthesis of nitric oxide in pregnant mice can interfere with the organ normal function and influence fertility parameters via causing abnormally and malformations in testis tissue, specially in the next generation.

Keywords

References

  1. Katzung BG, Masters SB, Trevor AJ. Basic and clinical pharmacology. 12th ed. New York, NY: McGraw-Hill Medical; 2012. p.331.
  2. Archer S. Measurement of nitric oxide in biological models. FASEB J 1993; 7(2): 349-60.
  3. Griffith OW, Stuehr DJ. Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 1995; 57: 707-36.
  4. Snyder SH. Nitric oxide. No endothelial NO. Nature 1995; 377(6546): 196-7.
  5. Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem 1994; 269(19): 13725-8.
  6. Nussler AK, Billiar TR. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 1993; 54(2): 171-8.
  7. Nussler AK, Billiar TR, Liu ZZ, Morris SM. Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production. J Biol Chem 1994; 269(2): 1257-61.
  8. Morris SM, Jr. Regulation of enzymes of urea and arginine synthesis. Annu Rev Nutr 1992; 12: 81-101.
  9. Sax HC, Hasselgren PO, Talamini MA, Edwards LL, Fischer JE. Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. J Surg Res 1988; 45(1): 50-5.
  10. Bogle RG, Baydoun AR, Pearson JD, Moncada S, Mann GE. L-arginine transport is increased in macrophages generating nitric oxide. Biochem J 1992; 284 (Pt 1): 15-8.
  11. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992; 6(12): 3051-64.
  12. Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998; 4(1): 3-24.
  13. Ariel I, Hochberg A, Shochina M. Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease. J Clin Pathol 1998; 51(6): 427-31.
  14. Fabregues F, Balasch J, Manau D, Creus M, Jimenez W, Carmona F, et al. Circulating levels of nitric oxide in successful and unsuccessful implantation after in vitro fertilization and embryo transfer. Relationship to estradiol and progesterone. Acta Obstet Gynecol Scand 2000; 79(7): 564-9.
  15. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod 2001; 64(4): 1033-40.
  16. Hefler LA, Reyes CA, O'Brien WE, Gregg AR. Perinatal development of endothelial nitric oxide synthase-deficient mice. Biol Reprod 2001; 64(2): 666-73.
  17. Azarnia M, Tahamtani Y, Rajabi M. An introduction to animal reproduction. Tehran, Iran: Jahad Daneshgahi Publications; 2007. p. 421-2.[In Persian].
  18. Adams ML, Meyer ER, Sewing BN, Cicero TJ. Effects of nitric oxide-related agents on rat testicular function. J Pharmacol Exp Ther 1994; 269(1): 230-7.
  19. Davidoff MS, Middendorff R, Mayer B, Holstein AF. Nitric oxide synthase (NOS-I) in Leydig cells of the human testis. Arch Histol Cytol 1995; 58(1): 17-30.
  20. Ehren I, Adolfsson J, Wiklund NP. Nitric oxide synthase activity in the human urogenital tract. Urol Res 1994; 22(5): 287-90.
  21. Burnett AL, Tillman SL, Chang TS, Epstein JI, Lowenstein CJ, Bredt DS, et al. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol 1993; 150(1): 73-6.
  22. Yu Y, Terada K, Nagasaki A, Takiguchi M, Mori M. Preparation of recombinant argininosuccinate synthetase and argininosuccinate lyase: expression of the enzymes in rat tissues. J Biochem 1995; 117(5): 952-7.
  23. Ewing JF, Maines MD. Distribution of constitutive (HO-2) and heat-inducible (HO-1) heme oxygenase isozymes in rat testes: HO-2 displays stage-specific expression in germ cells. Endocrinology 1995; 136(5): 2294-302.
  24. Zini A, O'Bryan MK, Magid MS, Schlegel PN. Immunohistochemical localization of endothelial nitric oxide synthase in human testis, epididymis, and vas deferens suggests a possible role for nitric oxide in spermatogenesis, sperm maturation, and programmed cell death. Biol Reprod 1996; 55(5): 935-41.
  25. Stephan JP, Guillemois C, Jegou B, Bauche F. Nitric oxide production by Sertoli cells in response to cytokines and lipopolysaccharide. Biochem Biophys Res Commun 1995; 213(1): 218-24.
  26. Tatsumi N, Fujisawa M, Kanzaki M, Okuda Y, Okada H, Arakawa S, et al. Nitric oxide production by cultured rat Leydig cells. Endocrinology 1997; 138(3): 994-8.
  27. Lancaster JR, Jr., Langrehr JM, Bergonia HA, Murase N, Simmons RL, Hoffman RA. EPR detection of heme and nonheme iron-containing protein nitrosylation by nitric oxide during rejection of rat heart allograft. J Biol Chem 1992; 267(16): 10994-8.
  28. Dashti N, Ansari M, Shabani M, Vardasti S, Mirsalehian A, Noori Mughehi MH, et al. The effect of nitric oxide donor in diabetic wound healing. Iran J Public Health 2003; 32(4): 59-63.
  29. Noori Mugahi SMH. Effect of nitric oxide (NO) system on cardiovascular development of rat embryo. Proceedings of the 10th International Congress of Toxicology; 2004 Jul 11-15; Tampere, Finland.
  30. Hogg N, Struck A, Goss SPA, Santanam N, Joseph J, Parthasamthy S, et al. Inhibition of macrophage-dependent low density lipoprotein oxidation by nitric oxide donors. J Lipid Res 1995; 36; 1756-62.
  31. Parivar K, Mohseni Koochesfahani H. Atlas of embryology and experimental embryology. Tehran, Iran: Jahad Daneshgahi Publication; 1994. [In Persian].
  32. Mohseni Koochesfahani H, Parivar K. Methods in histology, embryology and animal biology. Tehran, Iran: Alhossein Publications; 2000. [In Persian].
  33. Senayli A, Ekici F, Yilmaz R, Erdogan H. Measurement of hydroxyproline and nitric oxide, and comparison of sac fluid acidity in different inguinal pathologies. J Pediatr Urol 2013; 9(6 Pt B): 1122-5.
  34. Murad F. Regulation of cytosolic guanylyl cyclase by nitric oxide: the NO-cyclic GMP signal transduction system. Adv Pharmacol 1994; 26: 19-33.
  35. Khan FA, Scholtz EL, Chenier TS. The nitric oxide system in equine reproduction: Current status and future directions. J Equine Vet Sci 2015; 35(6): 481-7.
  36. Heuer O, Uckert S, Machtens SA, Stief CG, Tsikas D, Frolich JC, et al. Effects of various nitric oxide donating agents on the contractility and cyclic nucleotide turnover of human seminal vesicles in vitro. Urology 2002; 59(6): 958-62.
  37. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2): 109-42.
  38. Nee Pathak ND, Lal B. Seasonality in expression and distribution of nitric oxide synthase isoforms in the testis of the catfish, Clarias batrachus: role of nitric oxide in testosterone production. Comp Biochem Physiol C Toxicol Pharmacol 2010; 151(3): 286-93.
  39. Liman N, Alan E, Beyaz F, Gurbulak K. Endothelial and inducible nitric oxide synthase (NOS) immunoreactivity and NOS-associated NADPH-diaphorase histochemistry in the domestic cat (Felis catus) testis. Theriogenology 2013; 80(9): 1017-32.
  40. Banerjee A, Anjum S, Verma R, Krishna A. Alteration in expression of estrogen receptor isoforms alpha and beta, and aromatase in the testis and its relation with changes in nitric oxide during aging in mice. Steroids 2012; 77(6): 609-20.
  41. Ozokutan BH, Kucukaydin M, Muhtaroglu S, Tekin Y. The role of nitric oxide in testicular ischemia-reperfusion injury. J Pediatr Surg 2000; 35(1): 101-3.
  42. Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 1992; 89(16): 7674-7.
Journal of Isfahan Medical School
Volume 33, Issue 357 - Serial Number 357
September and October 2016
Pages 1871-1877

Files

History

  • Receive Date: 22 February 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics