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Characterization of the epididymis-specific lipocalin promoters to develop male contraceptive drugs in future

Research Project

Project/Area Number 18591792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTohoku University

Principal Investigator

SUZUKI Kichiya  Tohoku University, Tohoku University Hospital, Assistant Professor (30422116)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Takashi  Graduate School of Medicine, 大学院・医学系研究科, Associate Professor (20240666)
TERADA Yukihiro  Tohoku University Hospital, 病院, Associate Professor (10260431)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsepididymis / gene regulation / androgen receptor / sperm maturation / male reproduction / 精単上体 / プロモーター解析
Research Abstract

Sperm maturation process is one of the important function of the epididymis. If the process is specifically modulated, the sperm function for fertilizing ability may be disturbed. Therefore we hypothesized that characterization of epididymis-specific promoters would lead to the innovation of the male contraceptive drugs in future. As an initial study, we investigated the gene regulation mechanism of the Lipocalin 5 gene promoter. Lipocalin 5 is synthesized and secreted by the principal cells of the mouse middle/distal caput epididymidis and its regulation is androgen-dependent. We determined important cis-regulatory element between the 1.2 and 1.3 kb upstream region from transcription starting site using transgenic mice and epididymal cells. We also discovered that two androgen receptor binding sites and Foxal binding site exist in the 100 by fragment and that these molecules regulate gene expression of the Lipocalin 5 gene (Yu X, Suzuki K et al. Mol EndocrinoL 2007). Furthermore, we studied the Lipocalin 8 gene promoter as a second model, which is expressed in the initial segment and is regulated by transcription factors. We used same strategy as used for the Lipocalin 5 promoter study. Using transgenic mice, we established three lines carrying mutated Lipocalin 8 promoters ligated to the CAT reporter gene (3.0 kb, 1.7 kb, 0:3 kb). We confirmed that reporter gene expression level is decreased between 3.0 kb and 1.7 kb indicating that the 1.3-kb fragment contains important cis-regulatory element for the epididymis-specific gene expression, especially for the initial segment region.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (35 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 5 results) Presentation (16 results)

  • [Journal Article] Role of nicotinic and estrogen signaling during experimental acute and chronic bladder inflammation2008

    • Author(s)
      Martinez-Ferrer M
    • Journal Title

      Am J Pathol. 172

      Pages: 59-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Role of nicotinic and estrogen signaling during experimental acute and chronic bladder inflammation2008

    • Author(s)
      Martinez-Ferrer M, Iturregui JM, Uwamariya C, Starkman J, Sharif-Afshar AR, Suzuki K, Visedsindh W, Matusik RJ, Dmochowski RR, Bhowmick NA.
    • Journal Title

      Am J Pathol 172

      Pages: 59-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Epididymis-specific lipocalin promoters.2007

    • Author(s)
      Suzuki K
    • Journal Title

      Asian J Androl. 9

      Pages: 515-521

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Intestinal endometriosis complicated by ileal perforation after initiation of gonadotropin-releasing hormone agonist therapy.2007

    • Author(s)
      Saito S
    • Journal Title

      Fertil Steril. 88

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Epididymis-specific lipocalin promoters2007

    • Author(s)
      Suzuki K, Yu X, Chaurand P, Araki Y, Lareyre JJ, Caprioli RM, Orgebin-Crist M-C, Matusik RJ
    • Journal Title

      Asian J Androl 9

      Pages: 515-521

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Intestinal endometriosis complicated by ileal perforation after initiation of gonadotropin-releasing hormone agonist therapy2007

    • Author(s)
      Saito S, Murakami T, Suzuki K, Terada Y, Fukushima K, Moriya T
    • Journal Title

      Fertil Steril 88: 969

      Pages: 7-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Positive expression of the immunoglobulin superfamily pretein IZUMO on human sperm of severe male infertile patients.2007

    • Author(s)
      Hayasaka S, Terada Y. et al.
    • Journal Title

      Fertil. Steril. (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of photodynamic therapy using 5-aminolevulinic acid on cultured human adenomyosis-derived cells2007

    • Author(s)
      Suzuki-Kakisaka H, Murakami T. et al.
    • Journal Title

      Fertil. Steril. 87

      Pages: 33-38

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Epididymis-specific promoter-driven gene targeting-A transcription factor which regulates epididymis-specific gene expression2006

    • Author(s)
      Suzuki K
    • Journal Title

      Mol. Cell Endocrinol. 250

      Pages: 184-189

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The Role of Forkhead Box A2 (FOxa2) to Restrict Androgen Regulated Gene Expression of Lipocalin 5 in the Mouse Epidiymis2006

    • Author(s)
      YuX^*
    • Journal Title

      Mol Endocrinol. 20

      Pages: 2418-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Epididymis-specific promoter-driven gene targeting-A transcription factor which regulates epididymis-specific gene expression2006

    • Author(s)
      Suzuki K, Yu X, Chaurand P, Araki Y, Lareyre JJ, Caprioli RM, Robert J. Matusik RJ, Orgebin-Crist M-C
    • Journal Title

      Mol. Cell Endocrinol 250

      Pages: 184-189

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The Role of Forkhead Box A2 (Foxa2) to Restrict Androgen Regulated Gene Expression of Lipocalin 5 in the Mouse Epididymis2006

    • Author(s)
      Yu X^*, Suzuki K^*, Wang Y, Gupta A, Jin R, Orgebin-Crist MC, Matusik RJ
    • Journal Title

      Mol Endocrinol 20

      Pages: 2418-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Management of the pain associated with endometriosis : an update of the painful problems (review)2006

    • Author(s)
      Ozawa Y., Murakami T.et al.
    • Journal Title

      Tohoku J Exp Med 210

      Pages: 175-188

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Successful strategy for the hysteroscopic myomectomy of a submucous myoma arising from the uterine fundus.2006

    • Author(s)
      Murakami T. et al.
    • Journal Title

      Fertil. Steril. 86

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice.2006

    • Author(s)
      Ozawa Y., Murakami T.et al.
    • Journal Title

      FGertil. Steril. 84 suppl.

      Pages: 1146-51

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan.2006

    • Author(s)
      Chisaka H. et al.
    • Journal Title

      Tohoku J Exp Med 209

      Pages: 277-283

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The role of forkhead box A2 to restrict androgen-regulated gene expression of lipocalin 5 in the mouse epididymis2006

    • Author(s)
      Yu X, Suzuki K. et al.
    • Journal Title

      Mol. Endocrinology 20

      Pages: 2418-31

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pregnancy in a patient with retroperitoneal fibrosis who underwent in vitro fertilization.2006

    • Author(s)
      Nakamura S., Terada T.et al.
    • Journal Title

      Nophrol Dial Transplant 21

      Pages: 2669-2669

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lactation and risk of endometrial cancer in Japan : a case-control study.2006

    • Author(s)
      Okamura C. et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 109-115

    • Related Report
      2006 Annual Research Report
  • [Presentation] シンポジウム 精子成熟機構解明に向けた精巣上体特異的プロモーター解析2007

    • Author(s)
      鈴木吉也
    • Organizer
      第25回日本受精着床学会総会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Characterizaiton of the epididymis-specific promoter to study sperm maturation mechanism2007

    • Author(s)
      Invited Speaker Kichiya Suzuki
    • Organizer
      The 25th Annual meeting of Japan Society of Fertility and Implantation
    • Place of Presentation
      Sendai
    • Year and Date
      2007-08-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ポスター発表 精巣上体特異的レチノイン酸結合蛋白質KOマウスを用いた精巣上体炎モデル作製2007

    • Author(s)
      鈴木吉也
    • Organizer
      日本産婦人科学会総会
    • Place of Presentation
      京都
    • Year and Date
      2007-04-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 招待講演 精巣上体特異的リポカリンーその遺伝子発現制御機構-2007

    • Author(s)
      鈴木吉也
    • Organizer
      第38回精子研究会
    • Place of Presentation
      東大駒場キャンパス
    • Year and Date
      2007-01-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Epididymis-specific lipocalin - its gene expression mechanism-2007

    • Author(s)
      Invited Speaker Kichiya Suzuki
    • Organizer
      The 38th Sperm conference
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-01-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 招待講演Epididymis-Specific Lipocalin Promoter, Fourth International Workshop on Epididymis.2006

    • Author(s)
      鈴木吉也
    • Organizer
      Fourth International Workshop on Epididymis
    • Place of Presentation
      Chatel-Guyon, France
    • Year and Date
      2006-12-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Epididymis-Specific Lipocalin Promoter2006

    • Author(s)
      Invited speaker
    • Organizer
      Fourth International Workshop on Epididymis
    • Place of Presentation
      France
    • Year and Date
      2006-12-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 一般口演 精巣上体特異的レチノイン酸結合蛋白質欠損マウスの解析2006

    • Author(s)
      鈴木吉也
    • Organizer
      日本受精着床学会
    • Place of Presentation
      長野
    • Year and Date
      2006-09-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] An animal model for epididymitis using epididymal lipocalin KO mice2006

    • Organizer
      The 24th Annual meeting of Japan Society of Fertility and Implantation
    • Place of Presentation
      Nagano
    • Year and Date
      2006-09-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 一般口演 精巣上体特異的リポカリンKOマウスを用いた精巣上体炎モデル作製2006

    • Author(s)
      鈴木吉也
    • Organizer
      日本産婦人科学会北日本地方部会
    • Place of Presentation
      盛岡
    • Year and Date
      2006-09-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] An epididymitis model using epididymal lipocalin KO mice2006

    • Author(s)
      Oral presentation, Kichiya Suzuki
    • Organizer
      Annual meeting of North region Japan Society of Obstetrics and Gynecology
    • Place of Presentation
      Morioka
    • Year and Date
      2006-09-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] An animal model for epididymitis using epididymal lipocalin KO mice2006

    • Author(s)
      Poster presentation, Kichiya Suzuki
    • Organizer
      The 59th Annual meeting of Japan Society of Obstetrics and Gynecology
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-04-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 教育講演 精巣上体における蛋白質発現とプロテオミクス2006

    • Author(s)
      鈴木吉也
    • Organizer
      第518回日本産婦人科学会宮城地方部会集談会
    • Place of Presentation
      仙台
    • Year and Date
      2006-03-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Proteomics and protein expression in the epididymis2006

    • Author(s)
      Invited Speaker Kichiya Suzuki
    • Organizer
      Monthly Meeting of Japan Society of Obstetrics and Gynecology at Miyagi prefecture
    • Place of Presentation
      Sendai
    • Year and Date
      2006-03-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 講演Epididymis-specific promoter driven gene targeting.2006

    • Author(s)
      鈴木吉也
    • Organizer
      那須Spermカンファレンス
    • Place of Presentation
      那須
    • Year and Date
      2006-01-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Epididymis-specific promoter driven gene targeting2006

    • Author(s)
      Invited Speaker, Kichiya Suzuki
    • Organizer
      Nasu Sperm Conference
    • Place of Presentation
      Tochigi
    • Year and Date
      2006-01-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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