Analysis of the toxicological effects of phthalate esters on testes by administration, culture and transplantation methods

• Project/Area Number: 20380153
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied animal science
• Research Institution: The University of Tokyo
• Principal Investigator: KUROHMARU Masamichi 東京大学, 大学院・農学生命科学研究科, 教授 (00148636)
• Co-Investigator(Kenkyū-buntansha): KANAI Yoshiakira 東京大学, 大学院・農学生命科学研究科, 准教授 (30260326) ; OHSAKO Seiichiro 東京大学, 大学院・医学(系)研究科, 准教授 (00274837) ; MAEDA Seishi 兵庫医科大学, 医学部, 准教授 (10309445) ; TSUNEKAWA Naoki 東京大学, 大学院・農学生命科学研究科, 助教 (50431838)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: Di(n-butyl) phthalate / Di-iso-butyl phthalate / 精細胞 / アポトーシス / テストステロン濃度 / ステロイドホルモン合成酵素 / エストロゲン / エストロゲンレセプター / di(n-butyl)phthalate / di-iso-butyl phthalate / ICI 182,780 / estradiol-3-benzoate / 精巣内テストステロン / エストロゲン受容体 / 精巣内テストステロン濃度 / セルトリ細胞 / ビメンチンフィラメント / Di-n-butyl phthalate / Estrogen / Estrogen receptor / TUNEL法 / ステロイド合成酵素遺伝子 / 一日精子産生量

Research Abstract

Phthalate esters, widely used as a plasticizer in the manufacturing process of consumer products, are known to affect testes toxicologically. In the present study, di(n-butyl) phthalate(DBP) and di-iso-butyl phthalate(DiBP) which belong to phthalate esters, are used as materials, and the mechanism of their toxicological effects on testes are investigated by some different methods. As a result, DBP acts like an estrogen, and induces spermatogenic cell apoptosis, probably by activating estrogen receptors. On the other hand, DiBP induces spermatogenic cell apoptosis, probably independent of estrogen-mediated activity.

Research Products

• [Journal Article] Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis : A possible estrogenic effect of di(n-butyl) phthalate (2010)
  • Author(s): Alam, M. S., Ohsako, S., Matsuwaki, T., Zhu, X. B., Tsunekawa, N., Kanai, Y., Sone, H., Tohyama, C. and Kurohmaru, M.
  • Journal Title: Reproduction Volume: Vol.139 Pages: 427-437
  • Peer Reviewed
• [Journal Article] Di(n-butyl) phthalate induce vimentin filaments disruption in rat Sertoli cells : A possible relation with spermatogenic cell apoptosis (2010)
  • Author(s): Alam, M. S., Ohsako, S., Tay, T. W., Tsunekawa, N., Kanai, Y. and Kurohmaru, M.
  • Journal Title: Anat. Histol. Embryol Volume: Vol.39 Pages: 186-193
  • Peer Reviewed
• [Journal Article] Effects of di-iso-butyl phthalate on testes of prepubertal rats and mice (2010)
  • Author(s): Zhu, X.O., Tay, T.W., Andriana, B.B., Alam, M.S, Choi, E.K., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Okajimas Folia Anatomica Japonica Volume: 86 Pages: 129-136
  • NAID: 130004495072
  • Peer Reviewed
• [Journal Article] Single administration of di(n-butyl) phthalate delays spermatogenesis in prepubertal rats (2010)
  • Author(s): Alam, M.S., Andriana, B.B., Tay, T.W., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Tissue and Cell Volume: 42 Pages: 129-135
  • Peer Reviewed
• [Journal Article] Di(n-butyl) phthalate induces vimentin filaments disruption in rat Sertoli cells : a possible relation with spermatogenic cell apoptosis (2010)
  • Author(s): Alam, M.S., Ohsako, S., Tay, T.W., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Anatomia, Histologia, Embryologia Volume: 39 Pages: 186-193
  • Peer Reviewed
• [Journal Article] Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis : a possible estrogenic effect of di(n-butyl)phthalate (2010)
  • Author(s): Alam, M.S., Ohsako, S., Matsuwaki, T., Zhu, X.O., Tsunekawa, N., Kanai, Y., Sone, H., Tohyama, C., Kurohmaru, M.
  • Journal Title: Reproduction 139 Pages: 427-437
  • Peer Reviewed
• [Journal Article] Effects of di-iso-butyl phthalate on testes of prepubertal rats and mice (2010)
  • Author(s): Zhu, X.O., Tay, T.W., Andriana, B.B., Alam, M.S, Choi, E.K., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Okajimas Folia Anatomica Japonica 86(in press)
  • NAID: 130004495072
  • Peer Reviewed
• [Journal Article] Single administration of di(n-butyl)phthalate delays spermatogenesis in prepubertal rats (2010)
  • Author(s): Alam, M.S., Andriana, B.B., Tay, T.W., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Tissue and Cell (in press)
  • Peer Reviewed
• [Journal Article] Di(n-butyl)phthalate induces vimentin filaments disruption in rat Sertoli cells : a possible relation with spermatogenic cell apoptosis (2010)
  • Author(s): Alam, M.S., Ohsako, S., Tay, T.W., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Journal Title: Anatomia, Histologia, Embryologia (in press)
  • Peer Reviewed
• [Journal Article] A new preparation protocol for measurement of testicular sperm production (2008)
  • Author(s): Choi, E. K., Tsunekawa, N., Kanai, Y. and Kurohmaru, M.
  • Journal Title: J. Reprod. Dev. Volume: Vol.54, No.1 Pages: 90-93
  • NAID: 10021218720
  • Peer Reviewed
• [Journal Article] A new preparation protocol for measurement of testicular sperm production (2008)
  • Author(s): Choi, E. K., Tsunekawa, N, Kanai, Y., Kurohmaru, M.
  • Journal Title: Journal of Reproduction and Development 54 Pages: 90-93
  • NAID: 10021218720
  • Peer Reviewed
• [Journal Article] Single administration of di(n-butyl) phthalate delays spermatogenesis in prepubertal rats
  • Author(s): Alam, M. S., Andriana, B. B., Tay, T. W., Tsunekawa, N., Kanai, Y. and Kurohmaru, M.
  • Journal Title: Tissue & Cell Volume: Vol.42, No.2 Pages: 129-135
  • Peer Reviewed
• [Journal Article] Effects of di-iso-butyl phthalate on testes of prepubertal rats and mice
  • Author(s): Zhu, X. B., Tay, T. W., Andriana, B. B., Alam, M. S., Choi, E. K., Tsunekawa, N., Kanai, Y. and Kurohmaru, M.
  • Journal Title: Okajimas Folia Anat. Jpn. Volume: Vol.86, No.4 Pages: 129-136
  • NAID: 130004495072
  • Peer Reviewed
• [Presentation] Induction of spermatogenic cell apoptosis in prepubertal rat testes : an estrogenic effect of di(n-butyl)phthalate and its relationship with testicular steroidogenesis (2009)
  • Author(s): Alam, M.S., Ohsako, S., Tsunekawa, N.Kanai, Y., Tohyama, C., Kurohmaru, M.
  • Organizer: The 3^<rd> Congress of the Asian Association of Veterinary Anatomists
  • Place of Presentation: 清州(韓国)
  • Year and Date: 2009-11-05
• [Presentation] Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis : a possible estrogenic effect of di(n-butyl)phthalate (2009)
  • Author(s): Alam, M.S., Ohsako, S., Matsuwaki, T., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Organizer: 21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
  • Place of Presentation: 東京
  • Year and Date: 2009-10-25
• [Presentation] Di(n-butyl)phthalate(DBP)induces spermatogenic cell apoptosis via estrogenreceptor in prepubertal rat testes (2009)
  • Author(s): Alam, M.S., Ohsako, S., Tsunekawa, N.Kanai, Y., Kurohmaru, M.
  • Organizer: 第147回日本獣医学会学術集会
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-04-03
• [Presentation] Di(n-butyl) phthalate (DBP) induces spermatogenic cell apoptosis via estrogen receptor in prepubertal rat testes (2009)
  • Author(s): Mohammad Shah Alam,大迫誠一郎,祝暁波,恒川直樹,金井克晃,九郎丸正道
  • Organizer: 第147回日本獣医学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2009-04-03
• [Presentation] Di(n-butyl) phthalate(DBP) induces spermatogenic cell apoptosis via estrogen receptor in prepubertal rat testes (2009)
  • Author(s): Mohammad Shah Alam,大迫誠一郎,祝暁波,恒川直樹,金井克晃,九郎丸正道
  • Organizer: 第147回日本獣医学会
  • Place of Presentation: 宇都宮
• [Presentation] Induction of spermatogeni cell apoptosis in prepubertal rat testes : an estrogeniceffect of di(n-butyl) phthalate and its relationship with testicular steroidogenesis (2009)
  • Author(s): Alam, M. S., Ohsako, S., Tsunekawa, N. K anai, Y., Tohyama, C., Kurohmaru, M.
  • Organizer: The 3^<rd. Congress of the Asian Association of Veterinary Anatomists
  • Place of Presentation: Korea
• [Presentation] Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis : a possible estrogenic effect of di(n-butyl) phthalate (2009)
  • Author(s): Alam, M. S., Ohsako, S., Matsuwaki, T., Tsunekawa, N., Kanai, Y., Kurohmaru, M.
  • Organizer: 21^<st> Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
  • Place of Presentation: Tokyo
• [Presentation] Di-iso-butyl phthalate(DIBP)の精巣毒性における特異性の検討 (2008)
  • Author(s): 祝暁波,大迫誠一郎,Mohammad Shah Alam,大迫誠一郎,恒川直樹,金井克晃,遠山千春,九郎丸正道
  • Organizer: 第146回日本獣医学
  • Place of Presentation: 宮崎
  • Year and Date: 2008-09-25
• [Presentation] Di-iso-butyl phthalate(DIBP)の精巣毒性における特異性の検討 (2008)
  • Author(s): 祝暁波,大迫誠一郎, Mohammad Shah Alam,恒川直樹,金井克晃,遠山千春,九郎丸正道
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎