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2009 Fiscal Year Annual Research Report

周生期ホルモン曝露による標的器官への不可逆的影響の分子メカニズム

Research Project

Project/Area Number 19370027
Research InstitutionNational Institutes of Natural Sciences Okazaki Research Facilities

Principal Investigator

井口 泰泉  National Institutes of Natural Sciences Okazaki Research Facilities, 岡崎統合バイオサイエンスセンター, 教授 (90128588)

Keywords性ホルモン / 周生期曝露影響 / エピジェネテイクス / 不可逆的影響
Research Abstract

女性ホルモンであるエストロゲンは、生殖をはじめとした様々な局面で重要な機能を果たしているが、ひとたび成体のコントロールシステムが破綻をきたした場合、乳がんや子宮内膜症、不妊、骨粗しょう症などを引き起こすことが知られている。こうしたエストロゲンの制御システムの破綻の要因の一つとして、胎児期や幼若期におけるエストロゲン曝露による影響が懸念されている。本研究は、このエストロゲンによる制御システムの破綻の分子メカニズムを明らかにすることを目的としている。Hox遺伝子群に関しては、膣ではHox13のみが発現しており、出生直後の合成エストロゲン(DES)投与での発現変動は認められず、不可逆化との関連も認められなかった。さらに、出生直後のDES投与により不可逆化した膣で特異的に発現増加する遺伝子群、Areg,Ereg,Il1r2,Il1f5,ERα,ERβ,Hbegfを含む多くの遺伝子のメチル化状態を解析したが、細胞増殖に関連する遺伝子群に関してはメチル化の変動は認められなかった。しかし、不可逆化した膣ではERαの恒久的なリン酸化が起こっており、この現象に着目して解析した。不可逆的な反応を示す膣でメチル化レベルの高い遺伝子としてGrg1が見出された。マイクロアレイの解析からは、この遺伝子の発現は低下していた。Grg1を発現させるとエストロゲンで刺激した時のERαの活性が抑制されることが明らかとなった。この結果から、Grg1のメチル化レベルが高くなり、Greg1の発現が低下することにより、恒久的にERαの活性が高い状態で保たれていることも考えられる(Miyagawa et al.,未発表)。今後、さらに多くの遺伝子のメチル化状態と発現を比較するとともに、機能解析を行うことにより、遺伝子のメチル化と出生直後のエストロゲンによる組織不可逆化の関連を明らかにすることができると期待している。

  • Research Products

    (33 results)

All 2010 2009 Other

All Journal Article (27 results) (of which Peer Reviewed: 26 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Influences of sex, incubation temperature, and environmental quality on gonadal estrogen and androgen receptor messenger RNA expression in juvenile American alligators(Alligator mississippiensis)2010

    • Author(s)
      Moore, B.C., Milnes, M.R., Kohno, S., Katsu, Y., Iguchi, T., Guillette, L.J.
    • Journal Title

      Biol.Reprod. 82

      Pages: 194-201

    • Peer Reviewed
  • [Journal Article] Estrogen-dependent transactivation of amphioxus steroid hormone receptor via both estrogen- and androgen-response elements2010

    • Author(s)
      Katsu, Y., Kubokawa, K., Urushitani, H., Iguchi, T.
    • Journal Title

      Endocrinology 151

      Pages: 639-648

    • Peer Reviewed
  • [Journal Article] Estrogen receptor α is indispensable for the induction of persistent vaginal change by neonatal 5α-dihydrotestosterone exposure2010

    • Author(s)
      Miyagawa, S., Katsu, Y., Ohta, Y, Sudo, T., Lubahn, D.B., Iguchi, T.
    • Journal Title

      Biol.Reprod. 82

      Pages: 497-503

    • Peer Reviewed
  • [Journal Article] Sequence divergence and expression of a transformer gene in the branchiopod crustacean, Daphnia magna2010

    • Author(s)
      Kato, Y., Kobayashi, K., Oda, S., Tatarazako, N., Watanabe, H., Iguchi, T.
    • Journal Title

      Genomics 95

      Pages: 160-165

    • Peer Reviewed
  • [Journal Article] Establishment of a polyclonal antibody against the retinoid X receptor of the rock shell Thais clavigera and its application to rock shell tissues for imposex research2010

    • Author(s)
      Horiguchi, T., Urushitani, H., Ohta, Y., Iguchi, T., Shiraishi, H.
    • Journal Title

      Ecotoxicology 19

      Pages: 571-576

    • Peer Reviewed
  • [Journal Article] Introduction of foreign DNA into the water flea, Daphnia magna, by electroporation2010

    • Author(s)
      Kato, Y., Kobayashi, K., Watanabe, H., Iguchi, T.
    • Journal Title

      Ecotoxicology 19

      Pages: 589-592

    • Peer Reviewed
  • [Journal Article] Potential contributions of heat shock proteins to temperature-dependentsex determination in the American alligator2010

    • Author(s)
      Kohno, S., Katsu, Y., Urushitani, H., Ohta, Y., Iguchi, T., Guillette, L.J.Jr.
    • Journal Title

      Sex.Devel. 4

      Pages: 73-87

    • Peer Reviewed
  • [Journal Article] From reptilian phylogenomics to reptilian genomes : analyses of c-Jun and DJ-1 protooncogenes2010

    • Author(s)
      Katsu, Y., Braun, E.L., Guillette, L.J.Jr, Iguchi, T.
    • Journal Title

      Cytogenet.Genome Res. (In press)

    • Peer Reviewed
  • [Journal Article] Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors2010

    • Author(s)
      Katsu, Y., Taniguchi, E., Urushitani, H., Miyagawa, S., Takase, M., Kubokawa, K., Tooi, O., Oka, T., Santo, N., Myburgh, J., Matsuno, A., Iguchi, T.
    • Journal Title

      Gen.Comp.Endocrinol. (In press)

    • Peer Reviewed
  • [Journal Article] Involvement of insulin-like growth factor-I for the regulation of prolactin synthesis by estrogen and postnatal proliferation of lactotrophs in the mouse anterior pituitary2010

    • Author(s)
      Saitoh, Y., Hikake, T., Hayashi, S., Iguchi, T., Sato, T.
    • Journal Title

      Cell Tiss.Res. (In press)

    • Peer Reviewed
  • [Journal Article] Technique for the collection of clean urine from the Nile crocodile(Crocodylus niloticus)2010

    • Author(s)
      Myburgh, J.G., Huchzermeyer, F.W., Groenewald, H.B., Soley, J.T., Bekker, L.C., Booyse, D.G., Iguchi, T., Guillette, L.J.Jr.
    • Journal Title

      J.South African Vet.Assoc. (In press)

    • Peer Reviewed
  • [Journal Article] Differential involvement of IGF-I and estrogen on prolactin cells in the mouse anterior pituitary2010

    • Author(s)
      Hikake, T., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
    • Journal Title

      Exp.Biol.Med. (In peress)

    • Peer Reviewed
  • [Journal Article] Regulatory aspects on the use of fish embryos in environmental toxicology2010

    • Author(s)
      Halder, M., Leonard, M.A., Iguchi, T.Oris, J.T., Ryder, K., Belanger, S.E., Braunbeck, T.A., Embry, M.R., Whale, G., Norberg-King, T., Lillicrap, A.
    • Journal Title

      Integ.Environ.Assess.Manage. (In press)

    • Peer Reviewed
  • [Journal Article] Species extrapolation for the 21^<st> century. Species extrapolation for the 21^<st> century2010

    • Author(s)
      Celander, M.C., Goldstone, J.V., Denslow, N.D., Iguchi, T., Kille, P., Meyerhoff, R.D., Smith, B.A., Hutchinson, T.H., Wheeler, J.R.
    • Journal Title

      Environ.Toxicol.Chem. (In press)

    • Peer Reviewed
  • [Journal Article]2010

    • Author(s)
      Iguchi, T., Miyagawa, S., Sudo, T.
    • Journal Title

      Modern genetics of reproductive biology. In : Environmental Impacts on Reproductive Health and Fertility(Cambridge University Press)

      Pages: 249(60-71)

  • [Journal Article] Effects of diethylstilbestrol on ovarian follicle development in neonatal mice2009

    • Author(s)
      Kim, H., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
    • Journal Title

      Reprod.Toxicol. 27

      Pages: 55-62

    • Peer Reviewed
  • [Journal Article] Sexual reprogramming and estrogenic sensitization in wild fish exposed to ethinylestradiol2009

    • Author(s)
      Lange, A., Paull, G.C., Coe, T.S., Katsu, Y., Urushitani, H., Iguchi, T., Tyler, C.R.
    • Journal Title

      Environ.Sci.Technol. 43

      Pages: 1219-1225

    • Peer Reviewed
  • [Journal Article] Environmental health impacts of equine estrogens derived from hormone replacement therapy2009

    • Author(s)
      Tyler, C.R., Filby, A.L., Bickley, L.K., Cumming, R.I., Gibson, R., Labadie, P., Katsu, Y., Liney, K.E., Shears, J.A., Silva-Castros, V., Urushitani, H., Lange, A., Winter, M.J., Iguchi, T., Hill, E.M.
    • Journal Title

      Enviorn.Sci.Technol. 43

      Pages: 3897-3904

    • Peer Reviewed
  • [Journal Article] Thyroid histopathology assessments for the amphibian metamorphosis assay to detect thyroid-active substances2009

    • Author(s)
      Grim, K.C., Wolfe, M., Braunbeck, T., Iguchi, T., Ohta, Y., Tooi, O., Touart, L., Douglas, C., Wolf, D.C., Tietge, J.
    • Journal Title

      Tox.Pathol. 37

      Pages: 415-424

    • Peer Reviewed
  • [Journal Article] Genetic integrations of the androgen and Wnt/β-catenin pathways for the masculinization of external genitalia2009

    • Author(s)
      Miyagawa, S., Satoh, Y., Haraguchi, R., Suzuki, K., Iguchi, T., Taketo, M.M., Nakagata, N., Matsumoto, T., Takeyama, K., Kato, S., Yamada, G.
    • Journal Title

      Mol.Endocrinol. 23

      Pages: 871-880

    • Peer Reviewed
  • [Journal Article] Application of metamorphosis assay to a native Japanese amphibian species, Rana rugosa, for assessing effects of thyroid system affecting chemicals2009

    • Author(s)
      Oka, T., Miyahara, M., Yamamoto, J., Mitsui, N., Fujii, T., Tooi, O., Kashiwagi, K., Takase, M., Kashiwagi, A., Iguchi, T.
    • Journal Title

      Ecotoxicol.Environ.Safety 72

      Pages: 1400-1405

    • Peer Reviewed
  • [Journal Article] The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary2009

    • Author(s)
      Hikake, T., Hayashi, S., Iguchi T., Sato, T.
    • Journal Title

      J.Endocrinol. 203

      Pages: 231-240

    • Peer Reviewed
  • [Journal Article] Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries2009

    • Author(s)
      Kim, H., Nakajima, T., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
    • Journal Title

      Biol.Reprod. 81

      Pages: 1002-1009

    • Peer Reviewed
  • [Journal Article] Dosage dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program2009

    • Author(s)
      Miyagawa, S., Moon, A., Haraguchi, R., Inoue, C., Harada, M., Nakahara, C., Suzuki, K., Matsumaru, D., Kaneko, T., Matsuo, I., Yang, L., Taketo, M.M., Iguchi, T., Evans, S.M., Yamada, G.
    • Journal Title

      Development 136

      Pages: 3969-3978

    • Peer Reviewed
  • [Journal Article] Involvement of estrogen receptor β in the induction of polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol2009

    • Author(s)
      Kirigaya, A., Kim, H., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
    • Journal Title

      Zool.Sci. 26

      Pages: 704-712

    • Peer Reviewed
  • [Journal Article] Why public health agencies cannot depend upon good laboratory practices as a criterion for selecting data : The case of bisphenol A.2009

    • Author(s)
      Myers, J.P., vom Saal, F.S., Akingbemi, B.T., Arizono, K., Belcher, S., Colborn, T., Chahoud, I., Crain, D.A., Farabollini, F., Guillette, L.J.Jr., Hassold, T., Ho, S.-M., Hunt, P.A., Iguchi, T., Jobling, S., Kanno, J., Laufer, H., Marcus, M., McLachlan, J.A., Nadal, A., Oehlmann, J., Olea, N., Palanza, P., Parmigiani, S., Rubin, B.S., Schoenfelder, G., Sonnenschein, C., Soto, A.M., Talsness, C.E., Taylor, J.A., Vandenberg, L.N., Vandenbergh, J.G., Vogel, S., Watson, C.S., Welshons, W.V., Zoeller, R.T.
    • Journal Title

      Environ.Health Perspect. 117

      Pages: 309-315

    • Peer Reviewed
  • [Journal Article] Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring : hurdles, achievements and future outlook2009

    • Author(s)
      Van Aggelen, G., Ankley, G.T, Baldwin, W.S., Bearden, D.W., Benson, W.H., Chipman, J.K., Collette, T.W., Craft, J.A., Denslow, N.D., Embry, M.R., Falciani, F., George, S.G., Helbing, C.C., Hoekstra, P.F., Iguchi, T., Kagami, Y., Katsiadaki, I., Kille, P., Liu, L., Lord, P.G., McIntyre, T., O'Neill, A., Osachoff, H., Perkins, E.J., Santos, E.M., Skirrow, R.C., Snape, J.R., Tyler, C.R., Versteeg, D., Viant, M.R., Volz, D.C., Williams, T.D., Yu, L.
    • Journal Title

      Environ.Health Perspect. 118

      Pages: 1-5

    • Peer Reviewed
  • [Presentation] Genomic and epigenetic approaches for analysis of developmental effect of neonatal estrogen on mouse vagina2009

    • Author(s)
      Iguhi, T., Koide-Yohshida, S., Watanabe, H., Igarashi, K., Kannno, J., Miyagawa, S.
    • Organizer
      Horiba Symposium, University of Tokyo
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      20091026-20091027
  • [Presentation] Endocrine disruption across multiple animal species-common mechanism2009

    • Author(s)
      Iguchi, T.
    • Organizer
      e.hormone
    • Place of Presentation
      Tulane University, USA
    • Year and Date
      20091020-20091024
  • [Presentation] Modulation of sex determination by juvenile hormones and their analogs in Daphnia magna and endocrine disruption2009

    • Author(s)
      Iguchi, T., Kato, Y., Watanabe, H., Oda, S., Tatarazako, N.
    • Organizer
      International Conference on Comparative Endocrinology
    • Place of Presentation
      Hong Kong University, Hong Kong
    • Year and Date
      20090622-20090626
  • [Presentation] Endocrine disrupting contaminants and the developing ovary : alteredactivin/inhibin and steroid leads to modified follliculogenesis2009

    • Author(s)
      Guillette, L.J.Jr., Moore, B.C., Iguchi, T.
    • Organizer
      5^<th> Copenhagen Workshop on Endocrine Disrupters
    • Place of Presentation
      Rigshospirtalet, Copenhagen, Denmark
    • Year and Date
      20090520-20090522
  • [Presentation] Current status of the endocrine disruptor research in Japan and OECD including my own laboratory2009

    • Author(s)
      Iguchi, T.
    • Organizer
      International Symposium of Environmental Emerging Compound Measurement Technology and Management
    • Place of Presentation
      National Pingtung University, Taiwan
    • Year and Date
      2009-05-26
  • [Remarks]

    • URL

      http://www.nibb.ac.jp/bioenv1/index-j.html

URL: 

Published: 2011-06-16   Modified: 2016-04-21  

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