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Molecular biological mechanisms of early embryonic development and implantation

Research Project

Project/Area Number 09470365
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YOSHIMURA Yasunori  Keio University School of Medicine, Dept of OB/GYN, Professor, 医学部, 教授 (10129736)

Co-Investigator(Kenkyū-buntansha) KUJI Naoaki  Keio University School of Medicine, Dept of OB/GYN, 医学部, 助手 (80169987)
MIYAZAKI Toyohiko  Keio University School of Medicine, Dept of OB/GYN, 医学部, 講師 (20174162)
SUEOKA Kou  Keio University School of Medicine, Dept of OB/GYN, 医学部, 講師 (90162833)
田中 守  慶應義塾大学, 医学部, 助手 (20207145)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsendometrium / decidua / βィイD21ィエD2 integrin / implantation / hatching / attachment / outgrowth / β_1 integrin / β_1インテグリン
Research Abstract

In human embryo implantation, a large number of trophoblasts infiltrate through the decidua and extend as far as the superficial layer of the myometrium. We have demonstrated that human endometrial and decidual cells express components of receptors for ECM proteins, the βィイD21ィエD2 integrin family, on their surfaces and that the expression is a dynamic process related to the menstrual cycle. In addition, the expression of βィイD21ィエD2 integrins in human endometrium increases at the time of implantation and remains high in the decidua during early pregnancy. We developed assays for the attachment of mouse embryos and for trophoblastic spreading on cultured human decidual cells. The addition of antibodies directed against βィイD21ィエD2 and α integrin subunits to cultured decidual cells did not affect the rates of hatching or attachment of the blastocysts, whereas the outgrowth of embryos on the decidual cells was inhibited by their antibodies in a dose-dependent manner. Thus, βィイD21ィエD2 integr … More in in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation.
In the next experiment, the expression and function of focal adhesion kinase (FAK) in human decidual cells were investigated. This kinase is localized to focal adhesions in fibroblasts, and is phosphorylated on tyrosine in normal and src-transformed fibroblasts. Immunofluorescent staining revealed that the cultured decidual cells expressed high levels of FAK at the cell periphery. FAK co-localized with integrins in cellular focal adhesions. Treatment of decidual cells with herbimycin A, a tyrosine kinase inhibitor, did not affect the rate of hatching or attachment of blastocysts. However, the outgrowth of embryos on the decidual cells was inhibited by the addition of herbimycin A in a dose-dependent manner, implying that blastocyst attachment and outgrowth are mediated by different mechanisms. Thus, tyrosine phosphorylation of FAK on decidual cells may be important in development and differentiation following attachment.
The final experiment was undertaken to study the role of the RGD cross-linking region of integrin βィイD21ィエD2 subunit in embryo implantation. A peptide corresponding to integrin βィイD21ィエD2 [140-164] (DDL; DYPIDLYYLMDLSYSMKDDLENVKS) inhibited decidual cell attachment to FN-coated dishes in a dose-dependent manner. A variant integrin peptide in which Asp 157 and Asp 158 were replaced by Ala (AAL; DYPIDLYYLMDLSYSMKAALENVKS) did not affect decidual cell attachment to FN. Inhibition by DDL peptide was reversed by prior treatment with an RGD-containing peptide but not by prior treatment with an RGE-containing peptide. Treatment of decidual cells with synthetic peptides did not affect the rates of hatching and attachment of blastocysts. The outgrowth of embryos on decidual cells was inhibited by DDL peptide in a dose-dependent manner, but not by AAL peptide. These findings suggest that integrin βィイD21ィエD2 [140-164] on decidual cells may be important in embryonic development and differentiation following attachment. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Sueoka K, Yoshimura Y et al: "Integrins and reproductive physiology: expression and modulation infertilization, embryogenesis, and implantation"Fertil. Steril. 67. 799-811 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T, Yoshimura Y, et al: "Thioredoxin expression in the human endometrium during the menstrual cycle"Mol. Hum Reprod. 3. 989-993 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S, Yoshimura Y et al: "Functional role of focal adhesion kinase in the process if implantation"Mol Hum Reprod. 9. 907-914 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Murayama T, Yoshimura Y, et al: "Induction of thioredoxin, a redox-active protein, by steroid hormones during growth and differentiation of endometrial stomal cells in vitro"Endocrinology. 140. 365-372 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T. Yoshimura Y, et al: "Activation of c-Src kinase is associated with in vitro decidulization of human endometrial stromal cells"Endocrinology. 140. 2632-2636 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S. Yoshimura Y. et al: "Functional roll of Arg-Gly-Asp(RGD)-binding sites on β_1 integrin in embryo implantation using mouse blastocysts and human decidua."Biol. Reprod. 60. 1468-1474 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉村泰典、星和彦、武谷雄二 編: "不妊の基礎-病態の解明をめざして-"MEDICAL VIEW. 193 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 吉村泰典 編: "不妊診療プラクティス"中外医学社. 311 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S,Yoshimura Y et al.: "Function of βィイD21ィエD2 integrins on human decidual cells during implantation"Biol Reprod. 54. 745-752 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S,Yoshimura Y et al.: "Expression of βィイD21ィエD2 integrins in human endometrial stromal and decidual cells"J Clin Endocrinol Metab. 81. 1533-1540 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura Y: "Integrins expression, modulation, and signaling in fertilization, embryogenesis and implantttation"Keio J Med. 46. 16-24 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishimoto H, Natori M, Tanaka M, Miyazaki T, Kobayashi T, Yoshimura Y: "Role of oxygen-derived free radicals in fetal growth retardation induced by ischemia-reperfusion in rats"Am J Physiol. 272. H701-H705 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sueoka K, Shionkawa S, Miyazaki T, Kuji N, Tanaka M, Yoshimura Y:: "Integrins and reproductive physiology: expression and modulation in fertilization, embryogenesis, and implantation"Fertil Steril. 67. 799-811 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura Y: "The ovarian renin- angiotenisn system in reproductive physiology"ffront Neuroendocrinol. 18. 247-291 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamauchi J, Miyazaki T, Iwasaki S, Kishi I, Kuroshima M, Tei C, Yoshimura Y: "Effects of nitric oxide on ovulation and ovarian steroidogenesis and prostaglandin production in the rabbit"Endocrinology. 138. 3630-3637 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka M,Natori M, Ishimoto H, ,Miyakoshi K, Miyazaki T, Kobayashi T, Yoshimura Y: "Effects of a thromboxane inhiditor (OKY-046) in an ischemia- reperfusion model of intrauterine growth retardation in sprague-dawley rats"Biol Neonate. 72. 181-186 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inagaki N, Suzuki S, Nakatogawa N, Kitai H, Kuji N, Yoshimura Y,: "Separation of female chrommosomes is specifically induced by protein kinase C independent of the calcium pathway during fertilization of mouse eggs"J Mamm Ova Res. 14. 157-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inagaki N, Suzuki S. Kitai H,Nakatogawa N, Kitai H, Kuji N,Iwahashi K,Yoshimura Y: "Effects of KN-62, a selective inhiditor of calmodulin-dependent kinas II , on mouse oocyte activation"J Assist Reprod Genet. 14. 609-616 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jinno M, Katsumata Y, Hoshiai T, Nakamure Y, Matsumoto K ,Yoshimura Y,: ",A therapeutic role of prolactin supplementation in ovarian stimulation for in vitro fertilization: the dromocriptine-rebound method"J Clin Endocrinol Metab. 82. 3603-3611 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T, Kitaoka Y, Sachi Y, Nakanoin K, Hirota K, Shiozawa T,Yoshimura et al: "Thioredoxin expression in the human endometrium during the menstrual cycle"Mol Hum Reprod. 3. 989-993 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kaneko S, Kuroda Y, Takeuchi K, Nozawa S, Nozawa A, Oda T, Yoshimura Y: "Simultaneous determination of human sperm adenyl purine nucleotides and nucleoside by menas of high performance liquid chromatography-prelabel fluorescent detection system"Adv Reprod. 1. 29-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura et al: "Rola of βィイD21ィエD2 integrins in human endometrium and decidua during implantation"Horm Res. 50(suppl 2). 46-55 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tei C, Miyazaki T, Kuji N, Tanaka M, Sueoka K, Yoshimura Y: "Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro fertilization-embryo transfer"J Reprod Med. 43. 541-546 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S,Yoshimura et al: "Functional role of focal adhesion kinasein in the process of implantaion"Mol hum reprod. 9. 907-914 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshimura et al: "Insulin-Iike growth factors and ovarian physiology"J Obstet Gynaecol Res. 24. 305-323 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akaboshi K, Oda T, Yoshida j, Kohriyama S, Miyazaki T,Yoshimura Y: "The effects of gonadotropin-releasing hormone agonist on androstenedione production and follicular development during controlled ovarian hyperstimulation"J Assist reprod Gene. 15. 478-484 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki T, Tanaka M, Miyakoshi K, Minegishi K, Kasai K,Yoshimura y: "Power and color Doppler ultrasonography for the evaluation of the vasculature of the human corpus luteum"Hum Reprod. 13. 2836-2841 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyakoshi T, Tanaka M, Gabionza D, Takamatsu K, MiyazakiT, YuasaY, Mukai M, YoshimuraY: "Decidualizedovarian endometriosis mimicking malignancy"A.J.R.. 171. 1625-1626 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasi K, Miyazaki T, Minegishi K, Tanaka M, Yoshimura Y: "Effects of infertility therapeutics on maternal infection resulting in premature rupture of the membranes"Adv Obstet perinatol. 9. 107-111 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T, Sachi Y, Furuke K,Kitaoka Y, Kanzaki H,Yoshimura Y et al: "Induction of thioredoxin, a redox-active protein, by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro"Endocrinology. 140. 365-372 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T, Yoshimura Y et al: "Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells"Endocrinology. 140. 2632-2636 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shiokawa S,Yoshimura Y et al: "Functional role of Arg-Gly-Asp(RGD)-binding sites on βィイD21ィエD2 integrin in embryo implantation using mouse blastocysts and human decidua"Biol Reprod. 60. 1468-1474 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inagaki N, Sato K, Toyoshima K, Ito K, Kitai H, Gabionza D,Yoshimura Y: "Hysteroscopic selective salpingography"Fertil Steril. 72. 733-736 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakazawa K, Kanakura Y, Kometani K, Iwasaki S, Yoshimura Y: "Study on melatonin in human and rat placental tissue"Trophoblast Res. 467-474 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T, Yoshimura Y et al: "Tyrosine phosphorylation and subcellular localization of focal adhesion proteins during in vitro decidualization of human endometrial stromal cells"Endocrinology. 140. 5982-5990 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maruyama T,Yoshimura Y et al.: "Induction of thioredoxin,a redox-active protein,by ovarian steroid hormones during growth and differentiation of endometrial stromal cells in vitro"Endocrinology. 140. 365-372 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruyama T,Yoshimura Y et al.: "Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells"Endocrinology. 140. 2632-2636 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shiokawa S,Yoshimura Y et al.: "Functional role of Arg-Gly-Asp(RGD)-binding sites on β_1 integrin in embryo implantation using mouse blastocysts and human decidua"Biol Reprod. 60. 1468-1474 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inagaki N,Yoshimura Y et al.: "Hysteroscopic selective salpingography"Fertil Steril. 72. 733-736 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakazawa K,Yoshimura Y et al.: "Study on melatonin in human and rat placental tissue"Trophoblast Res. 467-474 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruyama T,Yoshimura Y et al.: "Tyrosine phosphorylation and subcellular localization of focal adhesion proteins during in vitro decidualization of human endometrial stromal cells"Endocrinology. 140. 5982-5900 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉村泰典 編: "不妊診療プラクティス"中外医学社. 311 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉村泰典: "不妊症の病態生理と診断治療"真興交易医書出版部. 156 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshimura Y et al.: "Role of β_1 integrins in human endometrium and decidua during implantation." Horm Res. 50(suppl 2). 46-55 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimura Y: "Insulin-like growth factors and ovarian physiology." J Obstet Gynaecol Res. 24. 305-323 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maruyama T,Yoshimura Y et al.: "Thioredoxin expression in the human endometrium during the menstrual cycle." Mol Hum Reprod. 3. 989-993 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sueoka K,Yoshimura Y et al.: "Falloposcopic tuboplasty for bilateral tubal occlusion. A novel infertility treatment as an alternative for in-vitro fertilization?" Hum Reprod. 13. 71-74 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tei C,Yoshimura Y et al.: "Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro fertilization-embryo transfer." J Reprod Med. 43. 541-546 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shiokawa S,Yoshimura Y et al.: "Functional role of focal adhesion kinase in the process of implantation." Mol Hum Reprod. 9. 907-914 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉村泰典、星和彦、武谷雄二編: "不妊の基礎-病態の解明をめざして-" MEDICAL VIEW, 193 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 星和彦、吉村泰典、武谷雄二編: "不妊の臨床-診断・治療の向上をめざして-" MEDICAL VIEW, 210 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimura Y et al.: "The ovarian renin-angiotensin system in reproductive physiology" Front Neuroendocrinol. 18. 247-291 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishimoto H, Yoshimura Y et al.: "Role of exygen-derived free radicals in fetal growth retardation induced by ischemia-reperfusion in rats." Am J Physiol. 272. H701-H705 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sueoka K, Yoshimura Y et al.: "Integrins and reproductive physiology: expression and modulation in fertilization,embryogenesis,and implantation." Fertil Steril. 67. 799-811 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshimura Y et al.: "Integrins:expression,modulation,and signaling in fertilization,embryoenesis and implantation." Keio J Med. 46. 16-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamauchi J, Yoshimura Y et al.: "Effects of nitric oxide on ovulation and ovarian steroidogenesis and prostaglandin production in the rabbit." Endocrinology. 138. 3630-3637 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka M, Yoshimura Y et al.: "Effects of a thromboxane synthetase inhibitor(OKY-046)in an ischemiareprerfusion model of intrauterine growth retardation in sprague-dawley rats." Biol Neonate. 72. 181-186 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka M,Yoshimura Y et al.: "Recent Advances on the Pathophysiology of Pregnancy" Organization Gestosis,Tokyo, 413 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aoki D,Yoshimura Y et al.: "Endometriosis Today" The Parthenon Publishing,New York, 478 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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