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The role of relaxin-like factor (RLF)/insulin-like factor 3 (INSL3) as germ cell anti-apoptotic and maturation factor on boar sperm production

Research Project

Project/Area Number 15K07691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Animal production science
Research InstitutionShizuoka University

Principal Investigator

Kohsaka Tetsuya  静岡大学, 農学部, 教授 (10186611)

Research Collaborator SASADA Hiroshi  
SHIBATA Masatoshi  
TERADA Kei  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsリラキシン / RLF / INSL3 / Passive immunization / Active immunization / Sperm production / Germ cell apoptosis / RLF/INSL3 / RLF不活性化 / 精子受精能 / cAMP/cGMP / 精子障害モデル / RNA干渉 / 不活性化 / 精子成熟 / Apoptosis / Testis
Outline of Final Research Achievements

This study was to produce model pigs neutralized endogenous RLF by immunization with RLF/INSL3 antibody and to investigate the mechanism of its action as germ cell anti-apoptotic and maturation factor. First, RLF inactivation resulted in a 4-fould increase in the frequency of apoptotic germ cells. Second, inactivation led to upregulation of the pro-apoptotic BAX and downregulation of the anti-apoptotic BCL2, and in turn activated the mitochondrial apoptotic pathway with induction of CASP3. Third, neutralization affected the development of epididymal muscle layer. Finally, inactivation had no effect on semen volume; however, it caused a significant reduction in sperm motility, concentration and quality compared with control. These results revealed that the RLF/INSL3 inactivation (neutralization) increases germ cell apoptosis and decreases in semen quality and sperm output, suggesting that RLF/INSL3 acts as an germ cell anti-apoptotic and maturation factor of sperm production.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 6 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Evidence for the role of INSL3 on sperm production in boars by passive immunisation.2018

    • Author(s)
      Minagawa I, Murata Y, Terada K, Shibata M, Park EY, Sasada H, Kohsaka T.
    • Journal Title

      Andrologia

      Volume: 50 Issue: 6 Pages: e13010-e13010

    • DOI

      10.1111/and.13010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin-like peptide 3 expressed in the silkworm possesses intrinsic disulfide bonds and full biological activity2017

    • Author(s)
      Miyazaki Takatsugu、Ishizaki Masaaki、Dohra Hideo、Park Sungjo、Terzic Andre、Kato Tatsuya、Kohsaka Tetsuya、Park Enoch Y.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17339-17339

    • DOI

      10.1038/s41598-017-17707-1

    • NAID

      120006371042

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional insulin-like factor 3 (INSL3) hormone-receptor system in the testes and spermatozoa of domestic ruminants and its potential as a predictor of sire fertility.2017

    • Author(s)
      Pitia AM, Uchiyama K, Sano H, Kinukawa M, Minato Y, Sasada H, Kohsaka T.
    • Journal Title

      Animal Science Journal

      Volume: 88 Issue: 4 Pages: 678-690

    • DOI

      10.1111/asj.12694

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression of insulin-like factor 3 hormone-receptor system in the reproductive organs of male goats.2015

    • Author(s)
      Pitia AM, Minagawa I, Uera N, Hamano K, Sugawara Y, Nagura Y, Hasegawa Y, Oyamada T, Sasada H, Kohsaka T.
    • Journal Title

      Cell Tissue Res

      Volume: 362 Issue: 2 Pages: 407-420

    • DOI

      10.1007/s00441-015-2206-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 受精におけるブタ卵胞液由来INSL3の精子側での作用2018

    • Author(s)
      飯塚真大・皆川至・山崎美悠・高橋綾乃・Ali M Pitia・佐々田比呂志・橋爪一善・高坂哲也
    • Organizer
      日本畜産学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 受動免疫法によるINSL3の中和化がブタ造精機能と精液性状に及ぼす影響2017

    • Author(s)
      皆川至、村田陽子、寺田圭、柴田昌利、佐々田比呂志、高坂哲也
    • Organizer
      日本畜産学会第122回大会
    • Place of Presentation
      神戸大学鶴甲第1キャンパス(兵庫県・神戸市)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 脂質過酸化を誘起させたブタ精子におけるリラキシンの影響2017

    • Author(s)
      高坂哲也・高橋綾乃・山崎美悠・飯塚真大・村田陽子・皆川至・佐々田比呂志
    • Organizer
      日本畜産学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Two relaxin family peptides, relaxin (RLN) and insulin-like factor 3 (INSL3) in porcine follicular fluid are involved in sperm fertility via their receptor signaling2016

    • Author(s)
      Murata Y, Minagawa I, Pitia AM, Shibata M, Sasada H, Hashizume K, Kohsaka T
    • Organizer
      The 17th Asian-Australasian Association of Animal Production Societies Animal Science Congress
    • Place of Presentation
      九州産業大学(福岡県・福岡市)
    • Year and Date
      2016-08-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Action of insulin-like factor 3 (INSL3) as a germ cell survival factor in boars2016

    • Author(s)
      Kohsaka T, Minagawa I, Sagata D, Pitia AM, Terada K, Shibata M, Hasegawa Y, Sasada H
    • Organizer
      The 17th Asian-Australasian Association of Animal Production Societies Animal Science Congress
    • Place of Presentation
      九州産業大学(福岡県・福岡市)
    • Year and Date
      2016-08-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The corpus luteum is a source and target of insulin-like factor 3 (INSL3) in pregnant goats2016

    • Author(s)
      Pitia AM, Minagawa I, Sasada H, Hashizume K, Kohsaka T
    • Organizer
      The 17th Asian-Australasian Association of Animal Production Societies Animal Science Congress
    • Place of Presentation
      九州産業大学(福岡県・福岡市)
    • Year and Date
      2016-08-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification, characterization, and possible function of a novel INSL3 receptor splice variant RXFP2.X6 in testes2015

    • Author(s)
      Tetsuya Kohsaka, Hiroshi Kohriki, Naoto Uera, Aya Tazawa, Yuta Katakura, Ali M Pitia, Itaru Minagawa, Yoshihisa Hasegawa, Hiroshi Sasada
    • Organizer
      7th International Congress on Relaxin and Related peptides
    • Place of Presentation
      クチン、マレーシア
    • Year and Date
      2015-09-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] SiRNA knockdown of a novel INSL3 receptor splice variant RXFP2.X6 alters INSL3-induced cAMP signaling in RXFP2-expressing HEK293 cells2015

    • Author(s)
      Yuta Katakura, Aya Tazawa, Itaru Minagawa, and Tetsuya Kohsaka
    • Organizer
      7th International Congress on Relaxin and Related peptides
    • Place of Presentation
      クチン、マレーシア
    • Year and Date
      2015-09-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effect of relaxin on ischemia-reperfusion injury in the rat testis2015

    • Author(s)
      Hiroyuki Sukigara, Masashi Morimoto,Shintaro Shimojima, Takuya Yoshida, Naoki Ikegaya, and Tetsuya Kohsaka
    • Organizer
      7th International Congress on Relaxin and Related peptides
    • Place of Presentation
      クチン、マレーシア
    • Year and Date
      2015-09-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Recent advances in research on the hormone INSL3 in male goats (In: Goat Science)2018

    • Author(s)
      Kohsaka T, Siqin, Minagawa I, Sasada H (編者:Sandor Kukovics)
    • Total Pages
      24
    • Publisher
      InTechOpen, London, UK
    • ISBN
      9781789232028
    • Related Report
      2017 Annual Research Report
  • [Remarks] 静岡大学教員データベース

    • URL

      https://tdb.shizuoka.ac.jp/RDB/public/Default2.aspx?id=10880&l=0

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Remarks] Google Scholar Citations

    • URL

      http://scholar.google.co.jp/citations?user=r7xYS3EAAAAJ&hl=ja

    • Related Report
      2016 Research-status Report 2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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