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Effects of indirubin a novel interval Ahreceptav ligand on the devepmeutard reproductive function of human fetus

Research Project

Project/Area Number 16510033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionSaitama Medical University

Principal Investigator

TAKAI Yasushi  Saitama Medical University, Medicine, Assistant Professor (60323549)

Co-Investigator(Kenkyū-buntansha) MIYAIRI Shinichi  Nihon University, Pharmacology, Professor (50209855)
OSUGA Yutaka  University of Tokyo, Medicine, Assistant Professor (80260496)
USUI Mayumi  Saitama Medical University, Medicine, Assistant Professor (60383270)
岩田 睦  埼玉医科大学, 医学部, 助手 (20364804)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsendocrine disrupting chemicals / indirubin / fetal exposure / oocyte / apoptosis / ダイオキシン類
Research Abstract

1. Maternal and fetal exposure to dioxins
The concentrations of dioxins (PCDDs, PCDFs and Co-PCBs) were determined in maternal and umbilical cord blood and amniotic fluid. There was a significant positive correlation between maternal age and maternal blood Co-PCBs, and also a significant positive correlation in total dioxin, PCDDs and Co-PCBs concentration between the maternal and umbilical cord blood, suggesting transplacental dioxin translocation. It was also shown that PCDDs and PCDFs are likely to accumulate in the lipid components in the amniotic fluid. Moreover, it was suggested that fetal dioxin exposure may affect fetal and neonatal thyroid function.
2. Effects of prenatal exposure to indirubin on offspring
Indirubin, which was found in human urine, has 50-times higher affinity to dioxin receptor (Ah receptor) and its biological function remains to be elucidated. Pregnant mice were administered on 14.5 dpc with 1) indirubin, 2) 7,8-benzoflavone (Ah receptor inhibitor), 3) indirubi … More n + 7,8-benzoflavone, and 4) DMSO alone. Birth weight of pups in groups 1) and 2) were significantly lower in those in 3) and 4), and follicle numbers in the ovaries on postnatal day 4 was lower in indirubin-treated groups.
3. Indirubin concentration in maternal urine and amniotic fluid
Indirubin concentration in the maternal blood in first (12-15 weeks), second (21-24 weeks), and third (33-36 weeks) trimester of their gestational period was determined by indirubin-specific ELJSA. Indirubin level in third trimester was significantly higher than those in first trimester. Birth weight, however, was not significantly correlated with the maternal indirubin level. Indirubin level was below the detectable limits in the amniotic fluid obtained in second and third trimester.
These results suggest that fetal exposure to indirubin may affect neonatal development and reproductive function, and that pregnant women are likely to be exposed to higher level of indirubin than non-pregnant women. However, it is also suggested that indirubin exposure of human fetus may remain insignificant. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005 2004

All Journal Article (27 results) (of which Peer Reviewed: 7 results) Presentation (6 results)

  • [Journal Article] Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells.122007

    • Author(s)
      Takai, Y.
    • Journal Title

      Apoptosis 12

      Pages: 791-800

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice2007

    • Author(s)
      Perez, G.I.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 229-234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice.2007

    • Author(s)
      Perez, G. I., et. al.
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 229-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Caspase-12 compensates for lack of caspase-2 and casi se-3 in female germ cells.2007

    • Author(s)
      Takai, Y., et. al.
    • Journal Title

      Apoptosis 12

      Pages: 791-800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. 12.2007

    • Author(s)
      Takai, Y.
    • Journal Title

      Apoptosis 12・4

      Pages: 791-800

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice.2007

    • Author(s)
      Perez, G.I.
    • Journal Title

      Proc Natl Acad Sci USA 104・12

      Pages: 229-34

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 内分泌撹乱物質汚染の性差,疾患との関連2006

    • Author(s)
      高井 泰
    • Journal Title

      ホルモンと臨床 54

      Pages: 191-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated Serum Bisphenol A Levels under Hyperandrogenic Conditions may be Caused by Decreased UDP-glucuronosyltransferase Activity2006

    • Author(s)
      Takeuchi, T.
    • Journal Title

      Endocr J 53

      Pages: 485-491

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Elevated Serum Bisphenol A Levels under Hyperandrogenic Conditions may be Caused by Decreased UDP-glucuronosyltransferase Activity.2006

    • Author(s)
      Takeuchi, T., et. al.
    • Journal Title

      Endocr J 53

      Pages: 485-491

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gender difference in serum levels of endocrine disrupting chemicals and its relationship with deseases.2006

    • Author(s)
      Takai, Y., et. al.
    • Journal Title

      Clin Endocrinol 54

      Pages: 191-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated Serum Bisphenol A Levels under Hyperandrogenic Conditions may be Caused by Decreased UDP-glucuronosyltransferase Activity.2006

    • Author(s)
      Takeuchi, T.
    • Journal Title

      Endocr J 53・4

      Pages: 485-91

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 内分泌攪乱物質汚染の性差、疾患との関連2006

    • Author(s)
      高井 泰, 竹内 亨, 堤 治
    • Journal Title

      ホルモンと臨床 54・3

      Pages: 191-195

    • NAID

      10017333351

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A central role for ceramide in the age-related acceleration of apoptosis in the female germline2005

    • Author(s)
      Perez, G.I.
    • Journal Title

      FASEB J 19

      Pages: 860-862

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Phosphorylation by Cdk1 induces Plk1-mediated vimentin phosphorylation during mitosis2005

    • Author(s)
      Yamaguchi, T.
    • Journal Title

      J Cell Biol 171

      Pages: 431-436

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 母児のダイオキシン類への曝露状況と次世代への影響2005

    • Author(s)
      高井 泰
    • Journal Title

      周産期学シンポジウム 23

      Pages: 35-43

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A central role for ceramide in the age-related acee of apoptosis in the female germline2005

    • Author(s)
      Perez, G. I., et. al.
    • Journal Title

      leration Faseb J 19

      Pages: 860-862

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phosphorylation by Cdkl induces Plkl-mediated vimentin phosphorylat ion during mitosis.2005

    • Author(s)
      Yamaguchi, T., et. al.
    • Journal Title

      J Cell Biol 171

      Pages: 431-436

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Maternal and fetal exposure to dlioxins and its effects Syaip Perinatol on our offspring2005

    • Author(s)
      Takai, Y.
    • Journal Title

      23

      Pages: 35-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A central role for ceramide in the age-related acceleration of apoptosis in the female germline2005

    • Author(s)
      Perez GI, Jurisicova A, Matikainen T, Moriyama T, Kim MR, Takai Y, Pru JK, Kolesnick RN, Tilly JT.
    • Journal Title

      FASEB J 19・7

      Pages: 860-862

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phosphorylation by Cdk1 induces Plk1-mediated vimentin phosphorylation during mitosis2005

    • Author(s)
      Yamaguchi, T, Goto H, Yokoyama T, Sillje H, Hanisch A, Uldschmid A, Takai Y, Oguri T, Nigg EA, Inagaki M
    • Journal Title

      J Cell Biol 171・3

      Pages: 431-436

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 母児のダイオキシン類への曝露状況と次世代への影響2005

    • Author(s)
      高井 泰, 生月弓子, 亀井良政, 竹内 亨, 堤 治, 武谷雄二
    • Journal Title

      周産期学シンポジウム 23

      Pages: 35-43

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Positive relationship between androgen and the endocrine disruptor,bisphenol A,in normal women and women with ovarian dysfunction2004

    • Author(s)
      Takeuchi, T.
    • Journal Title

      Endocr J 51

      Pages: 165-169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gender difference in serum bisphenol A levels may be caused by liver UDP-elucuronosvltransferase activity in rats2004

    • Author(s)
      Takeuchi, T.
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 549-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction.2004

    • Author(s)
      Takeuchi, T., et. al.
    • Journal Title

      Endocr J 51

      Pages: 165-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gender difference in serum bisphenol A levels maybe caused by liver UDP-glucijronosyltransferase activity in rats.2004

    • Author(s)
      Takeuchi, T., et. al.
    • Journal Title

      Biochem Biophys Res Common 325

      Pages: 549-554

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction2004

    • Author(s)
      Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y
    • Journal Title

      Endocr J 51・2

      Pages: 165-169

    • NAID

      80016601016

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gender difference in serum bisphenol A levels may be caused by liver UDP-glucuronosyltransferase activity in rats.2004

    • Author(s)
      Takeuchi, T., Tsutsumi, O., Nakamura N., Ikezuki, Y., Takai, Y., Yano, T., Taketani
    • Journal Title

      Biochem Biophys Res Commun 325・2

      Pages: 549-554

    • Related Report
      2004 Annual Research Report
  • [Presentation] ヒト胆汁中ダイオキシン類の検出と胆汁酸再吸収阻害剤による体内ダイオキシン排出の試み2005

    • Author(s)
      高井 泰
    • Organizer
      第78回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2005-07-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] Detection of dioxins in bile and its excretion studies using bile acid reabsorption inhibitors.2005

    • Author(s)
      Takai, Y., et. al.
    • Organizer
      78th Annual meeting of Japan Endocrine Society
    • Place of Presentation
      Tokyo
    • Year and Date
      2005-07-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] 母児のダイオキシン類への曝露状況と次世代への影響2005

    • Author(s)
      高井 泰
    • Organizer
      第23回日本周産期・新生児医学会周産期シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2005-01-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] Maternal and fetal exposure to dioxins and its effects on our offspring.2005

    • Author(s)
      Takai, Y.
    • Organizer
      23rd Symposium of Japan Society of Perinatal and Neonatal Medicine
    • Place of Presentation
      Tokyo
    • Year and Date
      2005-01-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] ヒト胆汁中ダイオキシン類の検出と胆道系悪性腫瘍との関連2004

    • Author(s)
      高井 泰
    • Organizer
      環境ホルモン学会第7回研究発表会
    • Place of Presentation
      名古屋
    • Year and Date
      2004-12-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] Detections of dioxing in bile and its relationship with biliary duct neoplasms.2004

    • Author(s)
      Takai, Y., et. al.
    • Organizer
      7th Annual meeting of Japan Society of Endocrine Disrupters Research
    • Place of Presentation
      Nagoya
    • Year and Date
      2004-12-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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