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Elucidation of the molecular basis of sex difference and sex-specific epigenome regulation and maintenance mechanism in mammalian gonads

Research Project

Project/Area Number 16K08072
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionKobe University

Principal Investigator

HOSHI NOBUHIKO  神戸大学, 先端融合研究環, 教授 (10209223)

Co-Investigator(Kenkyū-buntansha) 横山 俊史  神戸大学, 農学研究科, 助教 (10380156)
田渕 圭章  富山大学, 研究推進機構 研究推進総合支援センター, 教授 (20322109)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords性分化 / 生殖腺 / エピゲノム制御 / SRY / poschiavinus / 性差構築基盤 / 真性半陰陽 / 哺乳類 / 哺乳類性腺 / B6J / B6N / SOX9 / AMH / 生殖腺特異的エンハンサー / Sry / Dmrt1 / ヒストン修飾 / メチル化 / 転写制御 / 性差構築 / 性決定 / 分子基盤
Outline of Final Research Achievements

The establishment of sex differences begins with the determination of the fate of undifferentiated gonads to males (testis) or females (ovary) by "genetic control" with SRY as the master gene. Spatiotemporal sexual dimorphic expression of various sexual differentiation related factors is essential to maintain its male and female phenotype and function. As a result of detailed analysis of sex difference construction and failure mechanism of C57BL/6N-XYpos mouse, which show sex reversal phenotype created by us, 1) the genetic background of Y chromosome (SRY C-terminal) of C57BL/6 mouse may be the cause of sex reversal, 2) possibility that autosomal non-coding DNA region is involved, 3) possibility of involving new epigenetic factors, were suggested.

Academic Significance and Societal Importance of the Research Achievements

「性」は可逆性を有する分子基盤の上に成立している連続的な表現型であり,「遺伝的制御」にエピゲノム制御が加わることにより,生殖腺の「性」は変わりうる.すなわち,「性」は可逆性を有する分子基盤の上に成立している連続形質であることを支持する成果であり,性差を再定義する新しい概念に通じる.本研究成果は,生物の進化の過程を遡り,性腺の分化から哺乳類の誕生・進化の謎の一端を探求する意義あるものと考えられる.さらに,ヒトを含めた哺乳類の性分化およびその破綻機構の解明に新たな基礎的知見を加え,畜産学,獣医学および医科学の発展に大きく寄与するものと考えられる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Genetic differences between C57BL/6 substrains affect the process of testis differentiation in Y<sup>POS</sup> mice2019

    • Author(s)
      YOKOYAMA Toshifumi、MIURA Yuuka、YAMAMOTO Anzu、HASEGAWA Chinatsu、KAWANISHI Kohei、TAKADA Nanako、OMOTEHARA Takuya、HIRANO Tetsushi、MANTANI Yohei、MIKI Takanori、HOSHI Nobuhiko
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 4 Pages: 608-611

    • DOI

      10.1292/jvms.18-0621

    • NAID

      130007638718

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of reference genes for quantitative PCR analyses in developing mouse gonads2018

    • Author(s)
      YOKOYAMA Toshifumi、OMOTEHARA Takuya、HIRANO Tetsushi、KUBOTA Naoto、YANAI Shogo、HASEGAWA Chinatsu、TAKADA Tadashi、MANTANI Yohei、HOSHI Nobuhiko
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 10 Pages: 1534-1539

    • DOI

      10.1292/jvms.18-0417

    • NAID

      130007502949

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mechanisms underlying the effects of AMH on Müllerian duct regression in male mice2018

    • Author(s)
      Yamamoto A, Omotehara, Miura Y, Takada T, Yoneda N, Hirano T, Mantani Y, Kitagawa H, Yokoyama T, Hoshi N
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 80 Issue: 4 Pages: 557-567

    • DOI

      10.1292/jvms.18-0023

    • NAID

      130006708370

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a candidate enhancer for DMRT3 involved in spastic cerebral palsy pathogenesis.2018

    • Author(s)
      Kubota N, Yokoyama T, Hoshi N, Suyama M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 496 Issue: 1 Pages: 133-133

    • DOI

      10.1016/j.bbrc.2018.01.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice2017

    • Author(s)
      Yanai S, Hirano T, Omotehara T, Takada T, Yoneda N, Kubota N, Yamamoto A, Mantani Y, Yokoyama T, Kitagawa H, Hoshi N
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 79 Issue: 7 Pages: 1196-1203

    • DOI

      10.1292/jvms.17-0154

    • NAID

      130005712487

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the coelomic epithelial cells specific to the left testis in the chicken embryo.2017

    • Author(s)
      Omotehara T, Minami K, Mantani Y, Umemura Y, Nishida M, Hirano T, Yoshioka H, Kitagawa H, Yokoyama T, Hoshi N.
    • Journal Title

      Developmental Dynamics

      Volume: 246 Issue: 2 Pages: 148-156

    • DOI

      10.1002/dvdy.24469

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY<sup>POS</sup> mice2015

    • Author(s)
      UMEMURA Y., MIYAMOTO R., HASHIMOTO R., KINOSHITA K., OMOTEHARA T., NAGAHARA D., HIRANO T., KUBOTA N., MINAMI K., YANAI S., MASUDA N., YUASA H., MANTANI Y., MATSUO E., YOKOYAMA T., KITAGAWA H., HOSHI N.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 77 Issue: 12 Pages: 1587-1598

    • DOI

      10.1292/jvms.15-0292

    • NAID

      130005115330

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 性決定前のマウス未分化 XY 性腺の精巣化を誘導する器官培養法の確立とその組織学的評価2018

    • Author(s)
      長谷川千夏, 梅村ゆりあ, 三浦由佳, 川西航平, 高田菜々子, 大野周嗣, 万谷洋平, 横山 俊史, 星 信彦
    • Organizer
      第94回日本解剖学会近畿支部学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 性決定遺伝子発現前のマウス未分化XY性腺の精巣化を誘導する器官培養法2018

    • Author(s)
      長谷川千夏, 梅村ゆりあ, 三浦由佳, 川西航平, 高田菜々子, 大野周嗣, 万谷洋平, 横山 俊史, 星 信彦
    • Organizer
      関西実験動物研究会第140回研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ニワトリの発生過程に特徴的な生殖腺の左右差2017

    • Author(s)
      表原拓也,南 貴一,万谷洋平,朝克吉楽,梅村ゆりあ,西田美穂,平野哲史,青山裕彦,吉岡秀文,北川 浩,横山俊史,星 信彦
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎大学坂本キャンパス(長崎県長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 分子遺伝学が明かす男と女.2017

    • Author(s)
      星 信彦
    • Organizer
      第58回日本母性衛生学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 性決定・分化の多様性とその謎.2017

    • Author(s)
      星 信彦
    • Organizer
      第74回生体構造医学セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] The origin of the testicular cells in the chicken embryo.2017

    • Author(s)
      Omotehara T, Minami K, Mantani Y, Umemura Y, Nishida N, Hirano H, Yoshioka H, Kitagawa H, Yokoyama T, Itoh M, Hoshi N
    • Organizer
      Annual Meeting of the American Society for Reproductive Immunology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウスのミュラー管退行におけるAMH作用様式.2017

    • Author(s)
      山本杏,表原拓也,三浦由佳,川西航平,長谷川千夏,万谷洋平,北川 浩,横山俊史,星 信彦
    • Organizer
      第93回日本解剖学会近畿支部学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウスの亜系統差が生殖腺に及ぼす影響の遺伝学的研究2017

    • Author(s)
      三浦由佳,山本 杏,川西航平,長谷川千夏,横山俊史,星 信彦
    • Organizer
      第136回関西実験動物研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス胎子性腺における性分化関連遺伝子転写調節領域のDNAメチル化状態2016

    • Author(s)
      久保田直人,表原拓也,山本 杏,三浦由佳,平野哲史,南 貴一,柳井翔吾,高田 匡,米田直起,岩本 遥,万谷洋平,横山俊史,北川 浩,星 信彦
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス真性半陰陽個体のミュラー管退行とAMHの作用様式2016

    • Author(s)
      山本 杏,表原拓也,久保田直人,南 貴一,平野哲史,万谷洋平,北川 浩,横山俊史,星 信彦
    • Organizer
      第92回日本解剖学会近畿支部学術集会
    • Place of Presentation
      近畿大学東大阪キャンパス(大阪府東大阪市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Research-status Report
  • [Presentation] ニワトリ雌右性腺退縮メカニズムの解明2016

    • Author(s)
      南 貴一,表原拓也,田渕圭章,平野哲史,横山俊史,万谷洋平,北川 浩,星 信彦
    • Organizer
      第92回日本解剖学会近畿支部学術集会
    • Place of Presentation
      近畿大学東大阪キャンパス(大阪府東大阪市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス真性半陰陽個体におけるAMHの作用様式に関する組織学的解析2016

    • Author(s)
      山本 杏,表原拓也,久保田直人,南 貴一,広川千英,平野哲史,磯江美智子,柳井翔吾,高田 匡,米田直起,三浦由佳,岩本 遥,万谷洋平,北川 浩,横山俊史,星 信彦
    • Organizer
      第159回日本獣医学会学術集会
    • Place of Presentation
      日本大学 生物資源科学部(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Target and mechanism of neonicotinoid pesticides in birds and mammals.2016

    • Author(s)
      Hoshi N
    • Organizer
      Post-Neonics What Next ? Symposium
    • Place of Presentation
      早稲田大学(東京都新宿区)
    • Year and Date
      2016-06-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 地域固有性の発現による農業・農村の創造2018

    • Author(s)
      星 信彦
    • Total Pages
      207
    • Publisher
      つくば書房
    • ISBN
      9784811905327
    • Related Report
      2017 Research-status Report
  • [Book] 獣医組織学2017

    • Author(s)
      星 信彦
    • Total Pages
      378
    • Publisher
      学窓社
    • ISBN
      9784873627540
    • Related Report
      2017 Research-status Report
  • [Book] 獣医組織学 改訂第7版2017

    • Author(s)
      星 信彦
    • Total Pages
      362
    • Publisher
      学窓社
    • Related Report
      2016 Research-status Report
  • [Remarks] 形態機能学研究室ホームページ

    • URL

      http://morfunc.main.jp

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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