Morphology and functional analysis of mitochondria in uterine leiomyoma

• Project/Area Number: 26462475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Chiba University
• Principal Investigator: ISHIKAWA Hiroshi 千葉大学, 医学部附属病院, 医員 (70553973)
• Co-Investigator(Kenkyū-buntansha): 生水 真紀夫 千葉大学, 大学院医学研究院, 教授 (30226302)
• Research Collaborator: KOBAYASHI Tatsuya ; XU Linlin
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 子宮筋腫 / 低酸素 / HIF-1 / ミトコンドリア / 解糖 / HIF1

Outline of Final Research Achievements

Severe hypoxia may cause mitochondrial dysfunction in uterine leiomyoma; therefore, we clarified hypoxic responses in uterine leiomyoma. Expression of hypoxia inducible factor (HIF)-1α was significantly higher in uterine leiomyoma tissues than those in the adjacent myometrium. Hypoxia significantly induced HIF-1α protein expression and intranuclear distribution of HIF-1α in primary cultured uterine leiomyoma cells. Hypoxia also induced recruitment of HIF-1αbinding to the putative HIF response element on the promoter of HIF-responseive genes and subsequent mRNA expression of the HIF-responsive genes in uterine leiomyoma cells. Hypoxia significantly induced apoptosis of uterine leiomyoma cells. Taken together, hypoxia may induce HIF-mediated hypoxic responses in uterine leiomyoma.

Research Products

• [Journal Article] High serum progesterone associated with infertility in a woman with nonclassic congenital adrenal hyperplasia. (2017)
  • Author(s): Kawarai Y, Ishikawa H, Segawa T, Teramoto S, Tanaka T, Shozu M
  • Journal Title: J Obstet Gynaecol Res Volume: 印刷中 Issue: 5 Pages: 946-950
  • DOI: 10.1111/jog.13288
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Local injection of diluted vasopressin followed by suction curettage for cervical ectopic pregnancy. (2016)
  • Author(s): Ishikawa H, Unno Y, Omoto A, Shozu M.
  • Journal Title: Eur J Obstet Gynecol Reprod Biol Volume: 207 Pages: 173-177
  • DOI: 10.1016/j.ejogrb.2016.11.004
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 子宮筋腫発育についての最新の理解 (2016)
  • Author(s): 石川博士
  • Journal Title: 産科と婦人科 Volume: 83 Pages: 89-94
• [Journal Article] Spontaneous parasitic leiomyoma in a post-partum woman. (2016)
  • Author(s): Iida M, Ishikawa H, Shozu M
  • Journal Title: J Obstet Gynaecol Res Volume: 42 Issue: 12 Pages: 1874-1877
  • DOI: 10.1111/jog.13145
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Elevated serum progesterone levels in postmenopausal women with mucinous ovarian tumors (2016)
  • Author(s): Matsuoka A, Tate S, Nishikimi K, Ishikawa H, Shozu M
  • Journal Title: Menopause Volume: 23 Issue: 5 Pages: 544-549
  • DOI: 10.1097/gme.0000000000000587
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ovarian pregnancy associated with a fresh blastocyst transfer following in vitro fertilization (2015)
  • Author(s): Ishikawa H, Sanada M, Shozu M
  • Journal Title: J Obstet Gynaecol Res Volume: 41 Issue: 11 Pages: 1823-1825
  • DOI: 10.1111/jog.12790
  • Peer Reviewed
• [Journal Article] Tubal pregnancy associated with additional conception in a contralateral tube (2015)
  • Author(s): Ishikawa H, Kiyokawa T, Okayama J, Usui H, and Shozu M
  • Journal Title: J Obstet Gynaecol Res Volume: 41 Issue: 9 Pages: 1487-1490
  • DOI: 10.1111/jog.12744
  • Peer Reviewed
• [Presentation] Hypoxia induced cell proliferation and apoptosis in uterine leiomyoma and myometrial cells (2017)
  • Author(s): Ishikawa H, Nishiwaki T, Shozu M
  • Organizer: 第69回日本産科婦人科学会学術講演会
  • Place of Presentation: リーガロイヤルホテル広島（広島県 広島市）
  • Year and Date: 2017-04-13
• [Presentation] Giant ovarian endometriotic cyst associated with non-communicating rudimentary uterine horn in the absence of dysmenorrhea in an adolescent girl. (2016)
  • Author(s): Ishikawa H, Kawarai Y, Hayashida H, Kawano M, Shozu M
  • Organizer: 5th Asian Conference on Endometriosis
  • Place of Presentation: 大阪国際会議場（大阪府 大阪市）
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] Local injection of diluent vasopressin followed by suction curettage as initial treatment of cervical ectopic pregnancy. (2016)
  • Author(s): Ishikawa H,Shinno R, Omoto A, Unno Y, Usui H, Shozu M
  • Organizer: European society of Human Reproduction and Embryology 32nd annual meeting
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2016-06-03
  • Int'l Joint Research
• [Presentation] Hypoxic response mediated by hypoxia inducible factor-1α in uterine leiomyoma and myometrium (2016)
  • Author(s): Ishikawa H, Sone K, Wang G, Nishiwaki T, Shozu M
  • Organizer: 第68回日本産婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都 千代田区）
  • Year and Date: 2016-04-21
• [Presentation] Hypoxic response mediated by hypoxia inducible factor-1α in uterine leiomyoma and myometrium (2016)
  • Author(s): ISHIKAWA Hiroshi, SONE Kunizui, WANG Gui Wen, NISHIWAKI Tetsuji, SHOZU Makio
  • Organizer: 第68回日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-21
• [Presentation] Hypoxia induces hypoxia inducible factor-1α (HIF-1α) and its related gene expression in uterine leiomyoma (2016)
  • Author(s): Ishikawa H
  • Organizer: 3rd Congress of the Society of Endometriosis and Uterine disorders
  • Place of Presentation: Singapore, Singapore
  • Year and Date: 2016-04-05
  • Int'l Joint Research / Invited
• [Presentation] Hypoxic response mediated by hypoxia inducible factor-1α in uterine leiomyoma and myometrium (2016)
  • Author(s): Hiroshi Ishikawa, LinLin Xu, Tatsuya Kobayashi, Guiwen Wang, Makio Shozu
  • Organizer: Society for Reproductive Investigation 6３ｒｄ annual meeting
  • Place of Presentation: モントリオール、カナダ
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [Presentation] 子宮筋腫・子宮筋におけるHIF-1αの発現とHIFを介した低酸素反応の検討 (2015)
  • Author(s): 石川 博士、曽根 国瑞、徐 琳琳、小林 達也、生水 真紀夫
  • Organizer: 第33回内分泌代謝サマーセミナー
  • Place of Presentation: 柳川藩主立花亭御花（福岡県柳川市）
  • Year and Date: 2015-07-09
• [Presentation] 子宮筋腫では低酸素により低酸素誘導因子HIF1の発現が誘導される (2015)
  • Author(s): 石川 博士、徐 琳琳、曽根 国瑞、西脇 哲二、生水 真紀夫
  • Organizer: 第67回日本産科婦人科学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-10 – 2015-04-12
• [Presentation] 子宮筋腫では低酸素により低酸素誘導因子HIF1の発現が誘導される (2015)
  • Author(s): 石川博士、徐 琳琳、曽根国瑞、西脇哲二、生水真紀夫
  • Organizer: 第67回日本産科婦人科学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-10
• [Presentation] Hypoxia induces hypoxia- inducible factor-1 alpha in uterine leiomyoma cells (2015)
  • Author(s): Ishikawa H, Sone K, Xu L, Kobayashi T, Shozu M
  • Organizer: Society for Reproductive Investigation 62nd annual meeting
  • Place of Presentation: San Francisco, CA, United States
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 重症免疫不全マウスの腎被膜下移植子宮筋腫xenograftモデル (2015)
  • Author(s): 石川 博士、王 桂文、小林 達也、生水 真紀夫
  • Organizer: 第19回 日本生殖内分泌学会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府大阪市）
  • Year and Date: 2015-01-10