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. 1999 Apr;80(1-2):149–160. doi: 10.1038/sj.bjc.6690334

Characterization of the model for experimental testicular teratoma in 129/SvJ-mice

J Sundström 1,2,3, L J Pelliniemi 3, T Kuopio 4, E Veräjänkorva 1, K Fröjdman 6, V Harley 7, E Salminen 2, P Pöllänen 1,5
PMCID: PMC2363015  PMID: 10389991

Abstract

An animal model of experimental testicular teratoma has been established to study how a teratoma affects the host testis and how the host testis reacts against the teratoma. 129/SvJ-mice were used as experimental animals. To induce the experimental testicular teratoma, male gonadal ridges from 12-day-old 129/SvJ-mouse fetuses were grafted into the testes of adult mice for 1–12 weeks. The developing tumour was analysed by light and electron microscopy and by immunocytochemical localization of transcription factors SOX9 and c-kit, glial fibrillary acidic protein (GFAP) and type IV collagen. Testicular teratoma was observed in 36 out of 124 testes with implanted fetal gonadal ridges (frequency 29%). One spontaneous testicular teratoma was observed in this material from 70 male mice (1.5%). One week after implantation intracordal clusters of cells were seen in embryonic testicular cords of the graft as the first sign of testicular teratomas. Four weeks after implantation the embryonic testicular cords had totally disappeared from grafts with teratomas, and the tumour tissue had enlarged the testis and invaded the interstitium of the host testis. It consisted of solitary pieces of immature cartilage as well as of glial cells and of primitive neuroepithelium. Six to eight weeks after implantation the tumour tissue had expanded so that the enlarged testis could be detected by macroscopic enlargement of the scrotum. The testicular tissue of the host had practically disappeared, and only solitary disrupted seminiferous tubules of the host were seen surrounding the teratoma. Neuroepithelial structures of some teratomas cultured for 8 weeks had cells with a granular nucleus as a sign of obvious apoptosis. Eleven to 12 weeks after implantation the growth of the teratoma had stopped, and the histology corresponded to that of a mature cystic teratoma. GFAP, SOX9 and type IV collagen were strongly positive in some parts of the tumours cultured for 4 and 8 weeks, while only occasional c-kit-positive areas were observed in tumours cultured for 8 weeks. As conclusions: (1) the metastasizing capacity of the experimental testicular teratoma is very low during 12 weeks, but the behaviour of the tumour in the testicular tissue of the graft is invasive; (2) the growth of experimental testicular teratomas cease 6–8 weeks after implantation of the fetal gonadal ridges with the obvious apoptosis of the immature tissue components; (3) the model of experimental testicular teratoma in the mouse is suitable for studying how the teratoma affects the host testis and how the host testis reacts to teratoma. © 1999 Cancer Research Campaign

Keywords: animal model, mouse, testicular teratoma, characterization

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Selected References

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  1. Adami H. O., Bergström R., Möhner M., Zatoński W., Storm H., Ekbom A., Tretli S., Teppo L., Ziegler H., Rahu M. Testicular cancer in nine northern European countries. Int J Cancer. 1994 Oct 1;59(1):33–38. doi: 10.1002/ijc.2910590108. [DOI] [PubMed] [Google Scholar]
  2. Andrews P. W., Casper J., Damjanov I., Duggan-Keen M., Giwercman A., Hata J., von Keitz A., Looijenga L. H., Millán J. L., Oosterhuis J. W. Comparative analysis of cell surface antigens expressed by cell lines derived from human germ cell tumours. Int J Cancer. 1996 Jun 11;66(6):806–816. doi: 10.1002/(SICI)1097-0215(19960611)66:6<806::AID-IJC17>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  3. Andrews P. W. Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article. APMIS. 1998 Jan;106(1):158–168. doi: 10.1111/j.1699-0463.1998.tb01331.x. [DOI] [PubMed] [Google Scholar]
  4. Carlsen E., Giwercman A., Keiding N., Skakkebaek N. E. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609–613. doi: 10.1136/bmj.305.6854.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Finch B. W., Ephrussi B. RETENTION OF MULTIPLE DEVELOPMENTAL POTENTIALITIES BY CELLS OF A MOUSE TESTICULAR TERATOCARCINOMA DURING PROLONGED CULTURE in vitro AND THEIR EXTINCTION UPON HYBRIDIZATION WITH CELLS OF PERMANENT LINES. Proc Natl Acad Sci U S A. 1967 Mar;57(3):615–621. doi: 10.1073/pnas.57.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foidart J. M., Berman J. J., Paglia L., Rennard S., Abe S., Perantoni A., Martin G. R. Synthesis of fibronectin, laminin, and several collagens by a liver-derived epithelial line. Lab Invest. 1980 May;42(5):525–532. [PubMed] [Google Scholar]
  7. Foster J. W., Dominguez-Steglich M. A., Guioli S., Kwok C., Weller P. A., Stevanović M., Weissenbach J., Mansour S., Young I. D., Goodfellow P. N. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994 Dec 8;372(6506):525–530. doi: 10.1038/372525a0. [DOI] [PubMed] [Google Scholar]
  8. Friedrich T. D., Regenass U., Stevens L. C. Mouse genital ridges in organ culture: the effects of temperature on maturation and experimental induction of teratocarcinogenesis. Differentiation. 1983;24(1):60–64. doi: 10.1111/j.1432-0436.1983.tb01303.x. [DOI] [PubMed] [Google Scholar]
  9. Fröjdman K., Pelliniemi L. J., Virtanen I. Differential distribution of type IV collagen chains in the developing rat testis and ovary. Differentiation. 1998 Jul;63(3):125–130. doi: 10.1046/j.1432-0436.1998.6330125.x. [DOI] [PubMed] [Google Scholar]
  10. Gilliland F. D., Key C. R. Male genital cancers. Cancer. 1995 Jan 1;75(1 Suppl):295–315. doi: 10.1002/1097-0142(19950101)75:1+<295::aid-cncr2820751313>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  11. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  12. Martin G. R., Evans M. J. The morphology and growth of a pluripotent teratocarcinoma cell line and its derivatives in tissue culture. Cell. 1974 Jul;2(3):163–172. doi: 10.1016/0092-8674(74)90090-7. [DOI] [PubMed] [Google Scholar]
  13. Matin A., Collin G. B., Varnum D. S., Nadeau J. H. Testicular teratocarcinogenesis in mice--a review. APMIS. 1998 Jan;106(1):174–182. doi: 10.1111/j.1699-0463.1998.tb01333.x. [DOI] [PubMed] [Google Scholar]
  14. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  15. Morais da Silva S., Hacker A., Harley V., Goodfellow P., Swain A., Lovell-Badge R. Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nat Genet. 1996 Sep;14(1):62–68. doi: 10.1038/ng0996-62. [DOI] [PubMed] [Google Scholar]
  16. Mäenpä A., Kovanen P. E., Paetau A., Jäskeläinen J., Timonen T. Lymphocyte adhesion molecule ligands and extracellular matrix proteins in gliomas and normal brain: expression of VCAM-1 in gliomas. Acta Neuropathol. 1997 Sep;94(3):216–225. doi: 10.1007/s004010050696. [DOI] [PubMed] [Google Scholar]
  17. Noguchi T., Stevens L. C. Primordial germ cell proliferation in fetal testes in mouse strains with high and low incidences of congenital testicular teratomas. J Natl Cancer Inst. 1982 Oct;69(4):907–913. [PubMed] [Google Scholar]
  18. Oosterhuis J. W., Castedo S. M., de Jong B., Cornelisse C. J., Dam A., Sleijfer D. T., Schraffordt Koops H. Ploidy of primary germ cell tumors of the testis. Pathogenetic and clinical relevance. Lab Invest. 1989 Jan;60(1):14–21. [PubMed] [Google Scholar]
  21. Rajpert-De Meyts E., Skakkebaek N. E. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl. 1994 Apr;17(2):85–92. doi: 10.1111/j.1365-2605.1994.tb01225.x. [DOI] [PubMed] [Google Scholar]
  22. Ro J. Y., Dexeus F. H., el-Naggar A., Ayala A. G. Testicular germ cell tumors. Clinically relevant pathologic findings. Pathol Annu. 1991;26(Pt 2):59–87. [PubMed] [Google Scholar]
  23. STEMPAK J. G., WARD R. T. AN IMPROVED STAINING METHOD FOR ELECTRON MICROSCOPY. J Cell Biol. 1964 Sep;22:697–701. doi: 10.1083/jcb.22.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. STEVENS L. C. EXPERIMENTAL PRODUCTION OF TESTICULAR TERATOMAS IN MICE. Proc Natl Acad Sci U S A. 1964 Sep;52:654–661. doi: 10.1073/pnas.52.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. STEVENS L. C. Studies on transplantable testicular teratomas of strain 129 mice. J Natl Cancer Inst. 1958 Jun;20(6):1257–1275. doi: 10.1093/jnci/20.6.1257. [DOI] [PubMed] [Google Scholar]
  26. Solter D., Skreb N., Damjanov I. Extrauterine growth of mouse egg-cylinders results in malignant teratoma. Nature. 1970 Aug 1;227(5257):503–504. doi: 10.1038/227503a0. [DOI] [PubMed] [Google Scholar]
  27. Stevens L. C. A new inbred subline of mice (129-terSv) with a high incidence of spontaneous congenital testicular teratomas. J Natl Cancer Inst. 1973 Jan;50(1):235–242. doi: 10.1093/jnci/50.1.235. [DOI] [PubMed] [Google Scholar]
  28. Stevens L. C. Experimental production of testicular teratomas in mice of strains 129, A/He, and their F1 hybrids. J Natl Cancer Inst. 1970 Apr;44(4):923–929. [PubMed] [Google Scholar]
  29. Stevens L. C. Origin of testicular teratomas from primordial germ cells in mice. J Natl Cancer Inst. 1967 Apr;38(4):549–552. [PubMed] [Google Scholar]
  30. Stevens L. C. Spontaneous and experimentally induced testicular teratomas in mice. Cell Differ. 1984 Dec;15(2-4):69–74. doi: 10.1016/0045-6039(84)90054-x. [DOI] [PubMed] [Google Scholar]
  31. Stevens L. C. The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev Biol. 1970 Mar;21(3):364–382. doi: 10.1016/0012-1606(70)90130-2. [DOI] [PubMed] [Google Scholar]
  32. VENABLE J. H., COGGESHALL R. A SIMPLIFIED LEAD CITRATE STAIN FOR USE IN ELECTRON MICROSCOPY. J Cell Biol. 1965 May;25:407–408. doi: 10.1083/jcb.25.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Walt H., Oosterhuis J. W., Stevens L. C. Experimental testicular germ cell tumorigenesis in mouse strains with and without spontaneous tumours differs from development of germ cell tumours of the adult human testis. Int J Androl. 1993 Aug;16(4):267–271. doi: 10.1111/j.1365-2605.1993.tb01190.x. [DOI] [PubMed] [Google Scholar]
  34. Wang D., Enders G. C. Expression of a specific mouse germ cell nuclear antigen (GCNA1) by early embryonic testicular teratoma cells in 129/Sv-Sl/+ mice. Cancer Lett. 1996 Feb 27;100(1-2):31–36. doi: 10.1016/0304-3835(95)04068-4. [DOI] [PubMed] [Google Scholar]
  35. Zhao Q., Eberspaecher H., Lefebvre V., De Crombrugghe B. Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Dev Dyn. 1997 Aug;209(4):377–386. doi: 10.1002/(SICI)1097-0177(199708)209:4<377::AID-AJA5>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  36. Zheng T., Holford T. R., Ma Z., Ward B. A., Flannery J., Boyle P. Continuing increase in incidence of germ-cell testis cancer in young adults: experience from Connecticut, USA, 1935-1992. Int J Cancer. 1996 Mar 15;65(6):723–729. doi: 10.1002/(SICI)1097-0215(19960315)65:6<723::AID-IJC2>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  37. van Gurp R. J., Oosterhuis J. W., Kalscheuer V., Mariman E. C., Looijenga L. H. Biallelic expression of the H19 and IGF2 genes in human testicular germ cell tumors. J Natl Cancer Inst. 1994 Jul 20;86(14):1070–1075. doi: 10.1093/jnci/86.14.1070. [DOI] [PubMed] [Google Scholar]

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