子宮頸部の指標による子宮内膜の胚受容能の新規評価法の開発

2016 Fiscal Year Research-status Report

• Project/Area Number: 16K15701
• Research Institution: The University of Tokyo
• Principal Investigator: 廣田 泰 東京大学, 医学部附属病院, 講師 (40598653)
• Co-Investigator(Kenkyū-buntansha): 藤田 知子 東京大学, 医学部附属病院, 特別研究員 (60375441)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 子宮頸部上皮 / 子宮頸部スメア / 着床能 / 子宮 / バイオマーカー

Outline of Annual Research Achievements

着床能のバイオマーカーの候補分子抽出の目的で、RU486、ICI182780およびパラコートによる着床障害マウスモデルを用いて着床特異的に発現する子宮頸部上皮の分子を抽出を行った。具体的には、マウス着床前期から着床期にかけて子宮頸部上皮に発現するmRNAを時系列で比較し、着床期特異的に変動する遺伝子のうち、着床障害マウスで変動しない遺伝子群を抽出し、着床期特異的な320遺伝子を抽出できた。次に、着床に必須の子宮因子であるLIFが子宮頸部細胞の着床能のマーカーになるかどうかを検討した。マウス子宮頸部上皮のLIFは着床期に増加し着床障害マウスで低下し、ヒト子宮頸部上皮でも着床期にLIF発現が増加したことから、子宮頸部上皮のLIFが着床能のマーカーになりうると考えられた。子宮頸部スメアによる着床検査の臨床応用に向けた基礎的知見が得られた。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

マウスモデルを用いた研究が順調に行われており、その成果も順調に得られている。これらの成果をさらに発展させ、次年度以降の研究の更なる進展が期待できる。

Strategy for Future Research Activity

順調に進展し成果を上げているため、研究計画通りに進める予定とする。

Causes of Carryover

最終年度研究のまとめに際し、必要と思われる経費を残した

Expenditure Plan for Carryover Budget

.

Research Products

• [Int'l Joint Research] Wayne State University/Cincinnati Children's Hospital/Augusta University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Wayne State University/Cincinnati Children's Hospital/Augusta University
• [Journal Article] F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. (2017)
  • Author(s): Egashira M, Hirota Y, Shimizu-Hirota R, Saito-Fujita T, Haraguchi H, Matsumoto L, Matsuo M, Hiraoka T, Tanaka T, Akaeda S, Takehisa C, Saito-Kanatani M, Maeda K, Fujii T, Osuga Y.
  • Journal Title: Endocrinology Volume: 印刷中 Pages: 印刷中
  • DOI: https://doi.org/10.1210/en.2016-1886
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women. (2017)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Azhary JM, Yoshino O, Izumi G, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Endocrinology Volume: 158 Pages: 84-97
  • DOI: 10.1210/en.2016-1511
  • Peer Reviewed
• [Journal Article] STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation. (2016)
  • Author(s): Hiraoka T, Hirota Y, Saito-Fujita T, Matsuo M, Egashira M, Matsumoto L, Haraguchi H, Dey SK, Furukawa KS, Fujii T, Osuga Y.
  • Journal Title: JCI Insight Volume: 1 Pages: e87591
  • DOI: 10.1172/jci.insight.87591
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells. (2016)
  • Author(s): Makabe T, Koga K, Miyashita M, Takeuchi A, Sue F, Taguchi A, Urata Y, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Reprod Immunol Volume: 119 Pages: 44-48
  • DOI: 10.1016/j.jri.2016.12.002.
  • Peer Reviewed / Open Access
• [Journal Article] p53 coordinates decidual sestrin 2/AMPK/mTORC1 signaling to govern parturition timing. (2016)
  • Author(s): Deng W, Cha J, Yuan J, Haraguchi H, Bartos A, Leishman E, Viollet B, Bradshaw HB, Hirota Y, Dey SK.
  • Journal Title: J Clin Invest Volume: 126 Pages: 2941-2954
  • DOI: 10.1172/JCI87715.
  • Peer Reviewed / Open Access
• [Journal Article] Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis. (2016)
  • Author(s): Takeuchi A, Koga K, Miyashita M, Makabe T, Sue F, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 207 Pages: 157-161
  • DOI: 10.1016/j.ejogrb.2016.10.053.
  • Peer Reviewed
• [Journal Article] Development of ovarian cancer after excision of endometrioma. (2016)
  • Author(s): Haraguchi H, Koga K, Takamura M, Makabe T, Sue F, Miyashita M, Urata Y, Izumi G, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Oda K, Kawana K, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 106 Pages: 1432-1437.e2.
  • DOI: 10.1016/j.fertnstert.2016.07.1077.
  • Peer Reviewed
• [Journal Article] Mannose receptor is highly expressed by peritoneal dendritic cells in endometriosis. (2016)
  • Author(s): Izumi G, Koga K, Takamura M, Makabe T, Nagai M, Urata Y, Harada M, Hirata T, Hirota Y, Fujii T, Osuga Y.
  • Journal Title: Fertil Steril Volume: 107 Pages: 167-173.e2.
  • DOI: 10.1016/j.fertnstert.2016.09.036.
  • Peer Reviewed
• [Journal Article] Neutrophil depletion reduces endometriotic lesion formation in mice. (2016)
  • Author(s): Takamura M, Koga K, Izumi G, Urata Y, Nagai M, Hasegawa A, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol Volume: 76 Pages: 193-198
  • DOI: 10.1111/aji.12540.
  • Peer Reviewed
• [Journal Article] Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility. (2016)
  • Author(s): Bolnick AD, Bolnick JM, Kilburn BA, Stewart T, Oakes J, Rodriguez-Kovacs J, Kohan-Ghadr HR, Dai J, Diamond MP, Hirota Y, Drewlo S, Dey SK, Armant DR; NICHD National Cooperative Reproductive Medicine Network.
  • Journal Title: Hum Reprod Volume: 31 Pages: 2042-50
  • DOI: 10.1093/humrep/dew143.
  • Peer Reviewed / Open Access
• [Journal Article] Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis. (2016)
  • Author(s): Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, Nagai M, Urata Y, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: J Clin Endocrinol Metab Volume: 101 Pages: 2371-2379
  • DOI: 10.1210/jc.2016-1515.
  • Peer Reviewed
• [Journal Article] A potential role of endoplasmic reticulum stress in development of ovarian hyperstimulation syndrome. (2016)
  • Author(s): Takahashi N, Harada M, Hirota Y, Zhao L, Yoshino O, Urata Y, Izumi G, Takamura M, Hirata T, Koga K, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Mol Cell Endocrinol Volume: 428 Pages: 161-169
  • DOI: 10.1016/j.mce.2016.03.032.
  • Peer Reviewed
• [Journal Article] Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells. (2016)
  • Author(s): Taguchi A, Koga K, Kawana K, Makabe T, Sue F, Miyashita M, Yoshida M, Urata Y, Izumi G, Tkamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Fujii T, Osuga Y.
  • Journal Title: Am J Reprod Immunol Volume: 75 Pages: 486-492
  • DOI: 10.1111/aji.12489.
  • Peer Reviewed
• [Presentation] Activated IL6-STAT3 pathway in adenomyosis (2017)
  • Author(s): Hirota Y, Hiraoka T, Saito-Fujita T, Harada M, Fujii T, Osuga Y.
  • Organizer: World Conference of Endometriosis 2017
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2017-05-20
  • Int'l Joint Research
• [Presentation] IL6-STAT3経路の活性化が子宮腺筋症の進展に寄与する (2017)
  • Author(s): 廣田泰、平岡毅大、大須賀穣
  • Organizer: 第90回日本内分泌学会学術総会 シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2017-04-21
  • Invited
• [Presentation] 着床障害の分子機構の解明に基づく着床能の診断法と革新的治療技術の開発 (2017)
  • Author(s): 廣田泰
  • Organizer: 第69回日本産科婦人科学会学術講演会 シンポジウム
  • Place of Presentation: 広島
  • Year and Date: 2017-04-15
  • Invited
• [Presentation] 子宮の線維化：子宮腺筋症～IL6／STAT3経路の関与～ (2017)
  • Author(s): 廣田泰
  • Organizer: 第1回Frontier in basic and clinical research of fibrosis
  • Place of Presentation: 名古屋
  • Year and Date: 2017-03-04
  • Invited
• [Presentation] IL6-STAT3 signaling in adenomyosis (2016)
  • Author(s): Hirota Y.
  • Organizer: Asian Conference of Endometriosis 2016
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2016-09-23
  • Int'l Joint Research / Invited
• [Presentation] STAT3 promotes uterine regeneration in a mouse modelof decellularized uterine matrix transplantation (2016)
  • Author(s): Hirota Y.
  • Organizer: Gordon Research Conference on Mammalian Reproduction
  • Place of Presentation: Waterville Valley, NH, United States
  • Year and Date: 2016-08-24
  • Int'l Joint Research
• [Presentation] 黄体ホルモンによる子宮の胚受容能と着床の調節機構 (2016)
  • Author(s): 廣田泰
  • Organizer: 第5 回プロゲストーゲン研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-04
  • Invited
• [Presentation] 天然型プロゲステロンが着床に与える影響 (2016)
  • Author(s): 廣田泰
  • Organizer: 第3回最適な不妊治療を考える会
  • Place of Presentation: 東京
  • Year and Date: 2016-05-28
  • Invited
• [Remarks] 【プレスリリース】転写因子STAT3を介した子宮内膜の再構築と子宮の再生の仕組み
  • URL: http://www.h.u-tokyo.ac.jp/vcms_lf/release_20160603-1.pdf