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Evidence of the activation of unfolded protein response in granulosa and cumulus cells during follicular growth and maturation

Research Project

Project/Area Number 24791689
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

HARADA Miyuki  東京大学, 医学部附属病院, 助教 (70451812)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords卵巣 / 小胞体ストレス / 卵胞発育 / 卵胞成熟 / 顆粒膜細胞 / 卵子成熟
Research Abstract

Follicular growth and maturation are known to be regulated by intra-ovarian factors, although the mechanisms are still to be known. Recently, unfolded protain response (UPR) has been known to have essential roles in keeping homeostasis. In the present study, to test whether UPR in granulosa cells (GC) and cumulus cells (CC) is involved in the process of follicular growth and maturation, we examined the presence of UPR in GC during follicular growth and the association between UPR expression in CC and oocyte maturity. UPR-related genes, spliced form of X-box binding protein -1 (XBP1(S)) and heat shock 70kDa protein 5 (HSPA5), were expressed in mice GC of growing follicels, and their expression is stage-dependent. In addition, the expression levels of XBP1(S) mRNA in CC enclosing human mature oocytes were 2-fold higher than those in CC enclosing immature ooytes. These findings suggest that UPR is activated in GC during follicular growth, playing roles in follicular growth and maturation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2014 2013 2012

All Journal Article (19 results) (of which Peer Reviewed: 17 results) Presentation (12 results)

  • [Journal Article] Bone morphogenetic protein 7 increased vascular endothelial growth factor (VEGF)-a expression in human granulosa cells and VEGF receptor expression in endothelial cells.2014

    • Author(s)
      Akiyama I, Yoshino O et al.
    • Journal Title

      Reprod Sci.

      Volume: 21(4) Issue: 4 Pages: 477-82

    • DOI

      10.1177/1933719113503411

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for recurrence of mature cystic teratomas after surgical excision2013

    • Author(s)
      Harada M, Osuga Y, Fujimoto A, Fujimoto A, Yano T, Kozuma S
    • Journal Title

      Eur J Obstet Gynecol Reprod Biol

      Volume: 171 Pages: 325-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The significance of serum anti-Müllerian hormone (AMH) levels in patients over age 40 in first IVF treatment2013

    • Author(s)
      Tokura Y, Yoshino O, Ogura-Nose S, Motoyama H, Harada M, Osuga Y, Shmizu Y, Ohara M, Yorimitsu T, Nishii O, Kozuma S, Kawamura T.
    • Journal Title

      J Assist Reprod Genet.

      Volume: 30 Issue: 6 Pages: 821

    • DOI

      10.1007/s10815-013-9991-3

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-4 and prostaglandin E2 synergistically up-regulate 3β-hydroxysteroid dehydrogenase type 2 in endometrioma stromal cells2013

    • Author(s)
      Urata Y, Osuga Y, Akiyama I, Nagai M, Izumi G, Takamura M, Hasegawa A, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Kozuma S
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 98(4) Issue: 4 Pages: 1583-90

    • DOI

      10.1210/jc.2012-3475

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic Stretch Augments Production of Neutrophil Chemokines and Matrix Metalloproteinases-1 (MMP-1) from Human Decidual Cells, and the Production was Reduced by Progesterone.2013

    • Author(s)
      Zhao Y, Koga K, Osuga Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Yoshino O, Inoue S, Fujii T, Kozuma S
    • Journal Title

      Am J Reprod Immunol

      Volume: 69 Issue: 5 Pages: 454-462

    • DOI

      10.1111/aji.12092

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 採卵数の少ない症例に ICSI は必要か2013

    • Author(s)
      大井なぎさ, 原田美由紀, 藤本晃久, 大須賀穣
    • Journal Title

      産婦人科の実際

      Volume: 62 Pages: 1279-84

    • NAID

      40019806404

    • Related Report
      2013 Final Research Report
  • [Journal Article] 累積妊娠率から見た至適採卵数の検討2013

    • Author(s)
      大井なぎさ, 原田美由紀, 藤本晃久, 大石元, 平田哲也, 堤亮, 渡辺裕子, 大須賀穣, 藤井知行, 矢野哲, 上妻志郎
    • Journal Title

      日本受精着床学会誌

      Volume: 30 Pages: 65-9

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for recurrence of ovarian mature cystic teratomas after surgical excision.2013

    • Author(s)
      Harada M, Osuga Y, Fujimoto A, Fujimoto A, Fujii T, Yano T, Kozuma S
    • Journal Title

      Eur J Obstet Gyncol Reprod Biol.

      Volume: 171 Pages: 325-8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 採卵数の少ない症例にICSIは必要か2013

    • Author(s)
      大井なぎさ 原田美由紀 藤本晃久 大須賀穣
    • Journal Title

      産婦人科の実際

      Volume: 62 Pages: 1279-84

    • NAID

      40019806404

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The Localization and Regulation of Proprotein Convertase Subtilisin/Kexin (PCSK) 6 in Human Ovary2012

    • Author(s)
      Akiyama I, Yoshino O, Osuga Y, Shi J, Hirota Y, Hirata T, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
    • Journal Title

      Am J Reprod Immunol.

      Volume: 68 Issue: 6 Pages: 491

    • DOI

      10.1111/aji.12003

    • URL

      https://pure.teikyo.jp/en/publications/72e257c5-ea6f-41d3-8fc9-3257da1c1aff

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A is present in neutrophils in endometrioma and stimulates the secretion of growth-regulated oncogene-α (Gro-α) from endometrioma stromal cells2012

    • Author(s)
      Takamura M, Osuga Y, Izumi G, Yoshino O, Koga K, Saito A, Hirata T, Hirota Y, Harada M, Hasegawa A, Taketani Y
    • Journal Title

      Fertil Steril

      Volume: 98 Issue: 5 Pages: 1218-24

    • DOI

      10.1016/j.fertnstert.2012.07.1117

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Urata Y, Osuga Y, Izumi G, Takamura M, Koga K, Nagai M, Harada M, Hirata T, Hirota Y, Yoshino O, Taketani Y2012

    • Author(s)
      Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.
    • Journal Title

      Hum Reprod

      Volume: 27 Issue: 10 Pages: 3028-35

    • DOI

      10.1093/humrep/des291

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells2012

    • Author(s)
      Shi J, Yoshino O, Osuga Y, Akiyama I, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
    • Journal Title

      Fertil Steril.

      Volume: 97 Issue: 4 Pages: 979

    • DOI

      10.1016/j.fertnstert.2012.01.100

    • URL

      https://pure.teikyo.jp/en/publications/83d5155a-2476-4e53-a378-52fa2467d8e8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss2012

    • Author(s)
      Tsutsumi R, Fujimoto A, Osuga Y, Harada M, Takemura Y, Koizumi M, Yano T, Taketani Y.
    • Journal Title

      Gynecol Endocrinol

      Volume: 28 Issue: 6 Pages: 460

    • DOI

      10.3109/09513590.2011.633650

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The localization and regulation of proprotein convertase subtilisin/kexin (PCSK) 6 in human ovary.2012

    • Author(s)
      Akiyama I, Yoshino O, Osuga Y, Shi J, Hirota Y, Hirata T, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y
    • Journal Title

      Am J Reprod Immunol.

      Volume: 68 Pages: 491-8

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A is present in neutrophils in endometrioma and stimulates the secretion of growth-regulated oncogene-α (Gro-α) from endometrioma stromal cells.2012

    • Author(s)
      Takamura M, Osuga Y, Izumi G, Yoshino O, Koga K, Saito A, Hirata T, Hirota Y, Harada M, Hasegawa A, Taketani Y.
    • Journal Title

      Fertil Steril

      Volume: 98

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.2012

    • Author(s)
      Urata Y, Osuga Y, Izumi G, Takamura M, Koga K, Nagai M, Harada M, Hirata T, Hirota Y, Yoshino O, Taketani Y.
    • Journal Title

      Hum Reprod.

      Volume: 27 Pages: 3028-35

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP-6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells.2012

    • Author(s)
      Shi J, Yoshino O, Osuga Y, Akiyama I, Harada M, Koga K, Fujimoto A, Yano T, Taketani Y.
    • Journal Title

      Fertil Steril

      Volume: 97 Pages: 979-83

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss.2012

    • Author(s)
      Tsutsumi R, Fujimoto A, Osuga Y, Harada M, Takemura Y, Koizumi M, Yano T, Taketani Y.
    • Journal Title

      Gynecol Endocrinol

      Volume: 28 Pages: 460-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Evidence of the activation of unfolded protein response in cumulus cells during follicular growth and its possible role in oocyte maturation2013

    • Author(s)
      Harada M, Osuga Y, Yoshino O, Fujii T, Yano T, Kozuma S
    • Organizer
      95th The Endocrine Society's Annual Meeting
    • Place of Presentation
      サンフランシスコ(米国)
    • Related Report
      2013 Final Research Report
  • [Presentation] 卵巣成熟嚢胞性奇形腫の嚢腫摘出後の再発に関する検討2013

    • Author(s)
      藤本麻葉, 原田美由紀, 大須賀穣, 藤本晃久, 平池修, 藤井知行, 矢野哲, 上妻志郎
    • Organizer
      第65回日本産科婦人科学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 低用量ピルとジエノゲストの子宮内膜症性卵巣嚢胞摘出術後再発予防効果の比較検討2013

    • Author(s)
      能瀬さやか, 原田美由紀, 大須賀穣, 長谷川亜希子, 吉野修, 小泉美奈子, 有田白峰, 国府田きよ子, 松岡良
    • Organizer
      第65回日本産科婦人科学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      原田美由紀, 大須賀穣, 大井なぎさ, 堤亮, 平田哲也, 藤本晃久, 甲賀かをり, 平池修, 藤井知行
    • Organizer
      第53回日本産科婦人科内視鏡学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      吉新明日香, 原田美由紀, 大津洋, 藤本晃久, 大石元, 平田哲也, 堤亮, 大井なぎさ, 甲賀かをり, 平池修, 大須賀穣, 藤井知行
    • Organizer
      第58回日本生殖医学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] Evidence of the activation of unfolded protein response in cumulus cells during follicular growth and its possible role in oocyte maturation2013

    • Author(s)
      M Harada, Y Osuga, O Yoshino, T Fujii, T Yano, S Kozuma
    • Organizer
      95th The Endocrine Society's Annual Meeting
    • Place of Presentation
      San Fransisco, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 卵巣成熟嚢胞性奇形腫の嚢腫摘出術後の再発に関する検討2013

    • Author(s)
      藤本麻葉、原田美由紀、大須賀穣、藤本晃久、平池修、藤井知行、矢野哲、上妻志郎
    • Organizer
      第65回日本産科婦人科学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] 腹腔鏡下子宮内膜症性卵巣嚢胞摘出術の、卵巣機能に与える影響の検討2013

    • Author(s)
      原田美由紀、大須賀穣、大井なぎさ、堤亮、平田哲也、藤本晃久、甲賀かをり、平池修、藤井知行
    • Organizer
      第53回日本産科婦人科内視鏡学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] 凍結融解胚移植例と新鮮胚移植例の妊娠初期の血清hCG値推移の比較検討2013

    • Author(s)
      吉新明日香、原田美由紀、大津洋、藤本晃久、大石元、平田哲也、堤亮、大井なぎさ、甲賀かをり、平池修、大須賀穣、藤井知行
    • Organizer
      第58回日本生殖医学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 40歳以上の不妊患者におけるARTの予後規定因子の検討2012

    • Author(s)
      三宅友子, 原田美由紀, 藤本晃久, 大須賀穣, 大石元, 平田哲也, 長谷川亜希子, 藤井知行, 矢野哲, 上妻志郎
    • Organizer
      第57回日本生殖医学会
    • Place of Presentation
      長崎
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 採卵数の少ない症例に ICSI は必要か2012

    • Author(s)
      大井なぎさ, 原田美由紀, 藤本晃久, 大須賀穣, 大石元, 平田哲也, 堤亮, 森嶋かほる, 渡辺裕子, 増澤菜美, 藤井知行, 矢野哲, 上妻志郎
    • Organizer
      第57回日本生殖医学会
    • Place of Presentation
      長崎
    • Related Report
      2013 Final Research Report
  • [Presentation] 採卵数の少ない症例にICSIは必要か2012

    • Author(s)
      大井なぎさ、原田美由紀、藤本晃久、大須賀穣、大石元、平田哲也、堤亮、森嶋かほる、渡辺裕子、増澤菜美、藤井知行、矢野哲、上妻志郎
    • Organizer
      第57回日本生殖医学会
    • Place of Presentation
      長崎
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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