Molecular mechanism of irreversible changes in target organs induced by perinatal hormone exposure

2009 Fiscal Year Final Research Report

• Project/Area Number: 19370027
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: National Institutes of Natural Sciences Okazaki Research Facilities
• Principal Investigator: IGUCHI Taisen 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)
• Project Period (FY): 2007 – 2009
• Keywords: 組織形態

Research Abstract

Perinatal exposure of estrogens to mice during a critical period induces irreversible changes in various reproductive organs. Estrogen receptor α (ERα) has been demonstrated to be essential in induction of persistent changes in the mouse vagina. Microarray analyses demonstrate various up-regulated genes in the vagina of mice exposed perinatally to estrogens. Methylation status of growth factor related genes is not altered, however, one gene which suppress function of ERα is methylated and showing low expression. Methylation of this gene results in its low expression, thus, ERα is free from suppression, which may result in persistent activation of ERα. The persistently activated ERα induces expression of growth factor related genes which stimulate persistent cell proliferation in the mouse vagina.

Research Products

• [Journal Article] Estrogen receptorαis indispensable for the induction of persistent vaginal change by neonatal 5α-dihydrotestosterone exposure. (2010)
  • Author(s): Miyagawa, S., Katsu, Y., Ohta, Y, Sudo, T., Lubahn, D.B., Iguchi, T.
  • Journal Title: Biol. Reprod. 82 Pages: 497-503
• [Journal Article] Estrogen-dependent transactivation of amphioxus steroid hormone receptor via both estrogen-and androgen-response elements. (2010)
  • Author(s): Katsu, Y., Kubokawa, K., Urushitani, H., Iguchi, T.
  • Journal Title: Endocrinology 151 Pages: 639-648
• [Journal Article] Dosage dependent hedgehog signals integrated with Wnt/β-catenin signaling regulate external genitalia formation as an appendicular program. (2009)
  • Author(s): Miyagawa, S., 他Iguchi, T. (15名中3番目)
  • Journal Title: Development 136 Pages: 3969-3978
• [Journal Article] Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries. (2009)
  • Author(s): Kim, H., Nakajima, T., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
  • Journal Title: Biol. Reprod. 81 Pages: 1002-1009
• [Journal Article] The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary. (2009)
  • Author(s): Hikake, T., Hayashi, S., Iguchi, T., Sato, T.
  • Journal Title: J. Endocrinol. 203 Pages: 231-240
• [Journal Article] Genetic integrations of the androgen and Wnt/β-catenin pathways for the masculinization of external genitalia. (2009)
  • Author(s): Miyagawa, S., 他Iguchi, T. (11名中5番目)
  • Journal Title: Mol. Endocrinol. 23 Pages: 871-880
• [Journal Article] Effects of diethylstilbestrol on ovarian follicle development in neonatal mice. (2009)
  • Author(s): Kim, H., Hayashi, S., Chambon, P., Watanabe, H., Iguchi, T., Sato, T.
  • Journal Title: Reprod. Toxicol. 27 Pages: 55-62
• [Journal Article] Estrogen receptor subtypes selectively mediate female mouse reproductive abnormalities induced by neonatal exposure to estrogenic chemicals. (2008)
  • Author(s): Nakamura, T., Katsu, Y., Watanabe, H., Iguchi, T.
  • Journal Title: Toxicology 253 Pages: 117-124
• [Journal Article] Activation of steroid and xenobiotic receptor (SXR, NR112) and its orthologs in laboratory, toxicological, and genome model species. (2008)
  • Author(s): Milnes, M.R., Garcia, A., Grossman, E., Grun, F., Shiotsugu, J., Tabb, M.M., Kawashima, Y., Katsu, Y., Watanabe, H., Iguchi, T., Blumberg, B.
  • Journal Title: Environ. Health Perspect. 116 Pages: 880-885
• [Journal Article] Comparison of estrogen responsive genes in the mouse uterus, vagina and mammary gland. (2007)
  • Author(s): Suzuki, A., Urushitani, H., Watanabe, H., Sato, T., Iguchi, T., Kobayashi, T., Ohta, Y.
  • Journal Title: J. Vet. Med. Sci. 69 Pages: 725-731
• [Journal Article] Gene expression change in the Mullerian duct of the mouse fetus exposed to diethylstilbestrol in utero. (2007)
  • Author(s): Suzuki, A., Urushitani, H., Sato, T., Watanabe, H., Ohta, Y., Iguchi, T.
  • Journal Title: Exp. Biol. Med. 232 Pages: 503-514
• [Presentation] Genomic and epigenetic approaches for analysis of developmental effect of neonatal estrogen on mouse vagina. (2009)
  • Author(s): Iguchi, T., Koide-Yoshida, S., Watanabe, H., Igarashi, K. Kanno, J., Miyagawa, S.
  • Organizer: Horiba Symposium, University of Tokyo
  • Place of Presentation: Tokyo
  • Year and Date: 20091026-20091027
• [Book] Environmental Impacts on Reproductive Health and Fertility (2010)
  • Author(s): Iguchi, T., Miyagawa, S., Sudo, T.
  • Total Pages: 60-71
  • Publisher: Cambridge University Press
• [Book] Tool for Toxicology Assessment(Studying chemical effects and basic biology in vertebrates and invertebrates) (2008)
  • Author(s): Iguchi, T., Watanabe, H., Katsu, Y.
  • Total Pages: 143-158
  • Publisher: John Wiley & Sons
• [Book] Genomics in Regulatory Ecotoxicology: Applications and Challenges (2007)
  • Author(s): Tyler, C. R., Filby, A. L., Iguchi, T., Kramer, V., Larsson, J., van Aggelen, G., van Leeuwen, K., Viant, M., Tillet, D.
  • Total Pages: 33-62
  • Publisher: SETAC Press
• [Book] Examples of mosquitofish, roach and medaka(van der Spuy, Z. and Kempers, R.D. eds., What are the data on environmental contaminants disrupting reproductive function?) (2007)
  • Author(s): Iguchi, T.
  • Total Pages: 361-373
  • Publisher: Advances in Fertility Studies and Reproductive Medicine
• [Book] Genomic Approaches for Cross-Species Extrapolation in Toxicology.(Benson, W.H. and Di Giulio, R.T. (eds.), "Omic" Approaches in the context of environmental toxicology.) (2007)
  • Author(s): Cook, J., Iguchi, T., Linney, E., Miracle, A., Shaw, J., Viant, M., Zacharewski, T.
  • Total Pages: 1-31
  • Publisher: Taylor and Francis, CRC Press
• [Remarks]
  • URL: http://www.nibb.ac.jp/bioenv1/index-j.html