Advertisement

Archives of Toxicology

, Volume 63, Issue 4, pp 296–307 | Cite as

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene

  • Per Nylén
  • Ted Ebendal
  • Maria Eriksdotter-Nilsson
  • Tiiu Hansson
  • Andreas Henschen
  • Ann-Christin Johnson
  • Tony Kronevi
  • Ulrik Kvist
  • Nils O. Sjöstrand
  • Gunnar Höglund
  • Lars Olson
Original Articles

Abstract

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.

Key words

Testicular atrophy NGF Male germ cells spermatozoa Toluene Xylene n-Hexane Combined exposure 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdel-Rahman MS, Hetland LB, Couri D (1976) Toxicity and metabolism of methyl n-butyl ketone. Am Ind Hyg Assoc J 37: 95–102Google Scholar
  2. Altenkirch H, Mager J, Stoltenburg G, Helmbrecht J (1977) Toxic polyneuropathies after sniffing a glue thinner. J Neurol 214: 137–152Google Scholar
  3. Anthony DC, Boekelheide K, Anderson CW, Graham DG (1983) The effect of 3,4-dimethyl substitution on the neurotoxicity of 2,5-hexanedione II. Dimethyl substitution accelerates pyrrole formation and protein crosslinking. Toxicol Appl Pharmacol 71: 372–382Google Scholar
  4. Ayer-LeLievre C, Olson L, Ebendal T, Hallböök F, Shooter E, Person H (1988) Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc Natl Acad Sci USA 85: 2628–2632Google Scholar
  5. Bäckström B, Collins VP (1987) Cytoskeletal changes in axons of rats exposed to 2,5-hexanediol, demonstrated using monoclonal antibodies. Neurotoxicology 8: 85–96Google Scholar
  6. Boekelheide K (1987a) 2,5-Hexanedione alters microtubule assembly. I. Testicular atrophy, not nervous system toxicity, correlates with enhanced tubulin polymerization. Toxicol Appl Pharmacol 88: 370–382Google Scholar
  7. Boekelheide K (1987b) 2,5-Hexanedione alters microtubule assembly. II. Enhanced polymerization of crosslinked tubulin. Toxicol Appl Pharmacol 88: 383–396Google Scholar
  8. Boekelheide K (1988a) Rat testis during 2,5-hexanedione intoxication and recovery. I. Dose response and the reversibility of germ cell loss. Toxicol Appl Pharmacol 92: 18–27Google Scholar
  9. Boekelheide K (1988b) Rat testis during 2,5-hexanedione intoxication and recovery. II. Dynamics of pyrrole reactivity, tubulin content, and microtubule assembly. Toxicol Appl Pharmacol 92: 28–33Google Scholar
  10. Boekelheide K, Eveleth J (1988) The rate of 2,5-hexanedione intoxication, not total dose, determines the extent of testicular injury and altered microtubule assembly in the rat. Toxicol Appl Pharmacol 94: 76–83Google Scholar
  11. Cavanagh JB, Bennets RJ (1981) On the pattern of changes in the rat nervous system produced by 2,5-hexanediol. A topographical study by light microscopy. Brain 104: 297–318Google Scholar
  12. Chang CC (1964) A sensitive method for spectrophotofluorometric assay of catecholamines. Int J Neuropharmacol 3: 643–649Google Scholar
  13. Chapin RE, Norton RM, Popp JA, Bus JS (1982) The effects of 2,5-hexanedione on reproductive hormones and testicular enzyme activities in the F-344 rat. Toxicol Appl Pharmacol 62: 262–272Google Scholar
  14. Chapin RE, Morgan KT, Bus JS (1983) The morphogenesis of testicular degeneration induced in rats by orally administered 2,5-hexanedione. Exp Mol Pathol 38: 149–169Google Scholar
  15. Coons AH (1958) Fluorescent antibody methods. In: Danielli JF (ed) General cytochemical methods. Academic Press, New York pp 399–422Google Scholar
  16. Couri D, Hetland LB, O'Neill JJ, Ganansia M, Jackson DB, Gardier RW, Marks BH, Weiss H, Mendell JR, Saida K, Allen N, Chrisman CL (1974) Comments on a plastic industry neurotoxicity in relationship to methyl buthyl ketone. Proc 5th Conference on Environ Toxicol, pp 109–120Google Scholar
  17. Courtens JL, Delaleu B, Loir M (1983) Microtubules and spermiogenesis. In: André J (ed) The sperm cell. Martinus Nijhoff publishers, HaagGoogle Scholar
  18. DeCaprio AP (1987) n-Hexane neurotoxicity: a mechanism involving pyrrole adduct formation in axonal cytoskeletal protein. Neurotoxicology 8: 199–210Google Scholar
  19. DeCaprio AP, Olajos EJ, Weber P (1982) Covalent binding of a neurotoxic n-hexane metabolite: conversions of primary amines to substituted pyrrole adducts by 2,5-hexanedione. Toxicol Appl Pharmacol 65: 440–450Google Scholar
  20. DeMartino C, Malorni W, Amantini MC, Scorza Barcellona P, Frontali N (1987) Effects of respiratory treatment with N-hexane on rat testis morphology. I. A light microscopic study. Exp Mol Pathol 46: 199–216Google Scholar
  21. Ebendal T, Persson H, Larhammar D, Lundströmer K, Olson L (1989) Characterization of antibodies to synthetic nerve growth factor (NGF) and proNGF peptides. J Neurosci Res 22: 223–240Google Scholar
  22. Elofsson SA, Gamberale F, Hindmarsh T, Iregren A, Isaksson A, Johnsson I, Knave B, Lydahl E, Mindus P, Persson HE, Philipson B, Steby M, Struwe G, Söderman E, Wennberg A, Widen L (1980) Exposure to organic solvents. A cross-sectional epidemiological investigation on occupationally exposed car and industrial spray painters with special reference to the nervous system. Scand J Work Environ Health 6: 239–273Google Scholar
  23. Graham DG, Anthony DC, Boekelheide K, Marchman NA, Richards RG, Wolfram JW, Shaw BR (1982) Studies on molecular pathogenesis of n-hexane neuropathy. II. Evidence that pyrrole derivatization of lysyl residues leads to protein crosslinking. Toxicol Appl Pharmacol 64: 415–422Google Scholar
  24. Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1983) Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. Int Arch Occup Environ Health 53: 1–8Google Scholar
  25. Iwata M, Takeuchi Y, Hisanaga N, Ono Y (1984) Changes of n-hexane neurotoxicity and its urinary metabolites by longterm co-exposure with MEK or toluene. Int Arch Occup Environ Health 54: 273–281Google Scholar
  26. Johnson GD, Nogueira-Araujo GM (1981) A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods 43: 349–350Google Scholar
  27. Johnson AC, Juntunen L, Nylén P, Borg E, Höglund G (1988) Effect of interaction between noise and toluene on auditory function in the rat. Acta Otolaryngol (Stockh) 105: 56–63Google Scholar
  28. Jönsson M, Lindquist NG, Plöen L, Ekvärn S, Kronevi T (1979) Testicular lesions of coprine and benzocoprine. Toxicology 12: 89–100Google Scholar
  29. Mann T, Lutwak-Mann C (1981) In: Male reproductive function and semen. Springer Verlag, Berlin, Heidelberg, New YorkGoogle Scholar
  30. Mattison DR, Thorgeirsson SS (1978) Gonadal aryl hydrocarbon hydroxylase in rats and mice. Cancer Res 38: 1368–1373Google Scholar
  31. Ödkvist LM, Larsby B, Tham R, Aschan G (1979) On the mechanism of vestibular disturbances caused by industrial solvents. Adv Otorhinolaryngol 25: 167–172Google Scholar
  32. O'Donoghue JL, Krasagave WJ, Terhaar CJ (1978) Toxic effects of 2,5-hexanedione. Toxicol Appl Pharmacol 45: 269Google Scholar
  33. Olson L, Ayer-LeLievre C, Ebendal T, Seiger A (1987) Nerve growth factor-like immunoreactivities in rodent salivary glands and testis. Cell Tissue Res 248: 275–286Google Scholar
  34. Perbellini L, Leone R, Fracasso ME, Brugnone F, Venturini MS (1982) Metabolic interaction between n-hexane and toluene in vivo and in vitro. Int Arch Occup Environ Health 50: 351–358Google Scholar
  35. Platt JL, Michael AF (1983) Retardation of fading and enhancement of intensity of immunofluorescence by p-phenylenediamine. J Histochem Cytochem 31: 840–842Google Scholar
  36. Romeis B (1948) In: Romeis B (ed) Mikroskopische Technik. R Oldenburourg, MunichGoogle Scholar
  37. Saida K, Mendell JR, Weiss HS (1976) Peripheral nerve changes induced by methyl n-butyl ketone and potentiation by methyl ethyl ketone. J Neuropathol Exp Neurol 35: 207–225Google Scholar
  38. Shifman MA, Graham DG, Priest JW, Bouldin TW (1981) The neurotoxicity of 5-nonanone: preliminary report. Toxicol Lett 8: 283–288Google Scholar
  39. Sjöstrand NO, Swedin G (1976) Influence of age, growth, castration and testosterone treatment on the noradrenaline levels of ductus deferens and the auxiliary male reproductive glands of the rat. Acta Physiol Scand 98: 323–338Google Scholar
  40. Spencer PS, Schaumburg HS, Sabri MI, Veronesi B (1980) The enlarging view of hexacarbon neurotoxicity. CRC Crit Rev Toxicol 7: 279–356Google Scholar
  41. Takeuchi Y, Ono Y, Hisanaga N (1981) An experimental study on the combined effects of n-hexane and toluene on the peripheral nerve of the rat. Br J Indust Med 38: 14–19Google Scholar
  42. Toftgård R, Halpert J, Gustavsson JÅ (1983) Xylene induces a cytochrome P-450 isozyme in rat liver similar to the major isozyme induced by phenobarbital. Mol Pharmacol 23: 265–271Google Scholar
  43. Upreti RK, Shanker R (1987) 2,5-Hexanedione-induced immunomodulatory effect in mice. Environ Res 43: 48–59Google Scholar
  44. Upreti RK, Singh KP, Saxena AK, Shanker R (1986) Effect of 2,5-hexanedione on lymphoid organs of rats: a preliminary report. Environ Res 39: 188–198Google Scholar
  45. WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction. (1987) 2nd ed, Cambridge University PressGoogle Scholar
  46. Windemuller FJ, Ettema JH (1978) Effects of combined exposure to trichloroethylene and alcohol on mental capacity. Int Arch Occup Environ Health 41: 77–85Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Per Nylén
    • 1
  • Ted Ebendal
    • 2
  • Maria Eriksdotter-Nilsson
    • 3
  • Tiiu Hansson
    • 4
  • Andreas Henschen
    • 3
  • Ann-Christin Johnson
    • 1
  • Tony Kronevi
    • 5
  • Ulrik Kvist
    • 6
    • 7
  • Nils O. Sjöstrand
    • 7
  • Gunnar Höglund
    • 1
  • Lars Olson
    • 3
  1. 1.Department of NeuromedicineNational Institute of Occupational HealthSolnaSweden
  2. 2.Department of Developmental Biology, Biomedical CentreUppsala UniversityUppsalaSweden
  3. 3.Department of Histology and NeurobiologyKarolinska InstituteStockholmSweden
  4. 4.Department of Medical Nutrition, Karolinska InstituteHuddinge HospitalHuddingeSweden
  5. 5.Department of Occupational ToxicologyNational Institute of Occupational HealthSolnaSweden
  6. 6.Department of Clinical ChemistryUnit of andrology Karolinska HospitalStockholmSweden
  7. 7.Department of PhysiologyKarolinska InstituteStockholmSweden

Personalised recommendations