GENETICS AND DEVELOPMENTAL BIOLOGICAL ANALYSIS OF MECHANISMS INDUCING TESTICULAR TERATOCARCINOGENESIS IN PRIMORDIAL GERM CELLS IN MICE

• Project/Area Number: 12680809
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: SHIZUOKA UNIVERSITY
• Principal Investigator: NOGUCHI Motoko SHIZUOKA UNIVERSITY, FACULTY OF SCIENCE, ASSOCIATE PROFESSOR, 理学部, 助教授 (40021951)
• Co-Investigator(Kenkyū-buntansha): TOKUMOTO Toshinobu SHIZUOKA UNIVERSITY, FACULTY OF SCIENCE, ASSOCIATE PROFESSOR, 理学部, 助教授 (30273163)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: Testicular teratomas / Mouse embryo / Primordial germ cells / ter (teratoma) gene / ett1 (experimental testicular teratomas 1) gene / Germ-cell growth factor / Gonadal somatic cells / Apoptosis / マウス / テラトーマ原因遺伝子 / 染色体マッピング / 胎仔精巣 / 生殖細胞特異抗原 / ter変異遺伝子 / 原因遺伝子 / インプリンティング

Research Abstract

Testicular teratomas in mammals are congenital tumors composed of various kinds of tissues and embryonic multi-potent stem cells in testes. In the 129/Sv strain and its sublines susceptible to spontaneous testicular teratomas (STT), these stem cells are derived from primordial germ cells (PGC) in the fetal testes. The ter (teratoma, Chr. 18) mutation causes both the PGC deficiency and high incidence of STT in ter/ter males. About 90% of the grafts of the 129/Sv fetal testes differentiated experimental testicular teratomas (ETT). All of ter/ter males in ter congenic strains established by us have PGC deficient small testes without STT.
Then, in this project to clarify mechanisms underlying testicular teratocarcinogenesis in mice, the functions of the ter mutation, fetal testicular somatic cells and PGCs were examined and candidate genes responsible for ETT was searched genetically. Results obtained were summarized below.
1).The function of the ter gene inducing PGC deficiency was analyzed using "PGC-somatic cells co-culture systems" and conditioned medium (CM) from fetal ovarian and testicular somatic cells in the ter congenic mice. It is concluded that a novel ter-related PGC growth factor (designated as TER Factor, TERF) with soluble and membrane-bounded types supports PGC survival by inhibiting apoptosis in PGCs through developmental stages and that it is produced by ovarian and testicular somatic cells. It is also concluded that ter/ter somatic cells produce a default type of TERF, resulting in apoptotic death of ter/terPGCs with normal survivability and proliferation ability and sterility of ter/termales and females.
2).Fetal testicular somatic cells in 129/Sv-+/ter(+/+) mice may play key role(s) in the initial phase of induction of ETT.
3).A novel gene (designated as ett1, experimental testicular teratomas 1) responsible for ETT was mapped. Function of the ter nutation in testicular teratocarcinogenesis was discussed.

Research Products

• [Journal Article] The ter/ter gonadal somatic cells cause apoptosis in ter/ter primordial germ cells (PGCs) with normal survivability and proliferation ability in the mouse : Evidence from PGC-somatic cell "exchange-co-culture". (2001)
  • Author(s): Takabayashi, S., Nozaki, M., Ishikawa, K., Noguchi, M.
  • Journal Title: Zoological Science 18 Pages: 695-704
  • NAID: 110003371974
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Novel growth factor supporting survival of murine primordial germ cells : Evidence from conditioned medium of ter fetal gonadal somatic cells. (2001)
  • Author(s): Takabayashi, S., Sasaoka, Y., Yamashita, M., Tokumoto, T., Ishikawa, K., Noguchi, M.
  • Journal Title: Molecular Reproduction and Development 60 Pages: 384-396
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The ter/ter gonadal somatic cells cause apoptosis in ter/ter primordial germ cells (PGCs) with normal survivability and proliferation ability in the mouse : Evidence from PGC-somatic cell "exchange-co-culture". (2001)
  • Author(s): Takabayashi, S., Nozaki, M., Ishikawa, K.Noguchi, M.
  • Journal Title: Zoological Science 18(5) Pages: 695-704
  • NAID: 110003371974
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Novel growth factor supporting survival of murine primordial germ cells : Evidence from conditioned medium of ter fetal gonadal somatic cells. (2001)
  • Author(s): Takabayashi, S., Sasaoka, Y., Yamashita, M., Tokumoto, T., Ishikawa, K., Noguchi, M.
  • Journal Title: Molecular Reproduction and Development 60(3) Pages: 384-396
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Testicular somatic cells are responsible for experimental terato-carcinogenesis of primordial germ cells in reconstituted testes. (2000)
  • Author(s): Noguchi, M., Niwa, K., Kasai, T., Tsunesada, M., Sasaoka, Y., Kusakabe, M.
  • Journal Title: Journal of Reproduction and Development 46 Pages: 71-72
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development. (2000)
  • Author(s): Ueda, T., Abe, K., Miura, A., Noguchi, M., Sasaki, H.et al.
  • Journal Title: Genes to Cells 5 Pages: 649-659
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Testicular somatic cells are responsible for experimental teratocarcinogenesis of primordial gene cells in reconstituted mouse testes. (2000)
  • Author(s): Noguchi, M., Niwa, K., Kasai, T., Tsunesada, M., Sasaoka, Y., Kusakabe, M.
  • Journal Title: Journal of Reproduction and Development 46(Supplement) Pages: 71-72
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development. (2000)
  • Author(s): Ueda, T., Abe, K., Miura, A., Yuzuriha, M., Zubair, M., Noguchi, M., Niwa, K., Kawase, Y., Kono, T., Matsuda, Y., Fujimoto, H., Shibata, H., Hayashizaki, Y., Sasaki, H.
  • Journal Title: Genes to Cells 5(8) Pages: 649-659
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S.Takabayashi, M.Nozaki, K.Ishikawa, M.Noguchi: "The ter/ter gonadal somatic cells cause apoptosis inter/ter primordial germ cells (PG-Cs) with normal survivability and proliferation ability in the mouse : Evidence from PGC-somatic cell "exchange-co-culture""Zoological Science. 18(5). 695-704 (2001)
• [Publications] S.Takabayashi, T.Tokumoto, M.Noguchi, et al.: "Novel growth factor supporting survival of murine primordial germ cells : Evidence from conditioned medium of ter fetal gonadal somatic cells"Molecular Reproduction and Development. 60(3). 384-396 (2001)
• [Publications] T.Ueda,K.Abe,M.Noguchi,H.Sasaki et al: "The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development."Genes to Cells. 5(8). 649-659 (2000)