Induction of ovarian granulosa cells from mesenchymal stem cells for investigating the molecular mechanisms of their development.

• Project/Area Number: 15K10654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Yazawa Takashi 旭川医科大学, 医学部, 講師 (00334813)
• Co-Investigator(Kenkyū-buntansha): 谷口 隆信 旭川医科大学, 医学部, 教授 (60217130) ; 加藤 剛志 旭川医科大学, 医学部, 准教授 (60194833) ; 宇和田 淳介 旭川医科大学, 医学部, 助教 (70580314)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 顆粒膜細胞 / 幹細胞 / SF-1/Ad4BP / 一酸化窒素 / CYP19A1 / SF-1 / DNAマイクロアレイ

Outline of Final Research Achievements

Granulosa cells constitute the parts of somatic cells in follicles, and are essential for the development of oocytes. The purpose of this study is to induce granulosa cells from stem cells and precursor cells for revealing the molecular mechanism of their development. We established granulosa-like cells from mesenchymal stem cells and undifferentiated granulosa cell tumor-derived cells by introducing SF-1/Ad4BP. Using these systems, it was revealed the genes involved in the differentiation of granulosa cells, and identified a major androgen in human plasma.

Research Products

• [Int'l Joint Research] University of Rajshah(バングラデシュ)
• [Journal Article] Diethylstilbestrol administration inhibits theca cell androgen and granulosa cell estrogen production in immature rat ovary (2017)
  • Author(s): Imamichi, Y., Sekiguchi, T., Kitano, T., Kajitani, T., Okada, R., Inaoka, Y., Miyamoto, K., Uwada, J., Takahashi, S., Nemoto, T., Mano, A., Khan, M.R.I., Islam, M.T., Yuhki, K., Kashiwagi, H., Ushikubi, F., Suzuki, N., Taniguchi, T., Yazawa, T.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 8374-8374
  • DOI: 10.1038/s41598-017-08780-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of muscarinic receptors prevents TNF-α-mediated intestinal epithelial barrier disruption through p38 MAPK (2017)
  • Author(s): Uwada Junsuke、Yazawa Takashi、Islam Md Tariqul、Khan Md Rafiqul Islam、Krug Susanne M.、Fromm Michael、Karaki Shin-ichiro、Suzuki Yuichi、Kuwahara Atsukazu、Yoshiki Hatsumi、Sada Kiyonao、Muramatsu Ikunobu、Taniguchi Takanobu
  • Journal Title: Cellular Signalling Volume: 35 Pages: 188-196
  • DOI: 10.1016/j.cellsig.2017.04.007
  • NAID: 120006491645
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 11-ketotestosterone is a major androgen produced in human gonads (2016)
  • Author(s): Imamichi, Y., Yuhki, K.-I., Orisaka, M., Kitano, T., Mukai, K., Ushikubi, F., Taniguchi, T., Umezawa, A., Miyamoto, K., Yazawa, T.
  • Journal Title: J. Clin. Endocrinol. Metab. Volume: 101 Issue: 10 Pages: 3582-3591
  • DOI: 10.1210/jc.2016-2311
  • NAID: 120006348221
  • Peer Reviewed
• [Journal Article] Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review] (2016)
  • Author(s): 1.Yazawa, T., Imamichi, Y., Miyamoto, M., Khan, MR., Uwada, J., Umezawa, A., Taniguchi, T.:
  • Journal Title: Endocrine Journal Volume: 63 Issue: 11 Pages: 943-951
  • DOI: 10.1507/endocrj.EJ16-0373
  • NAID: 130005170487
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biology and Medicine of Peptide and Steroid Hormones: Special Issue for the Fifth Workshop on Peptide & Hormone Research (2015)
  • Author(s): Yazawa T
  • Journal Title: American Journal of Life Sciences Volume: 3 Issue: 3 Pages: 1-2
  • DOI: 10.11648/j.ajls.s.2015030302.11
  • Open Access
• [Journal Article] Overviews of Stem Cells for Gonadal and Adreanl Steroidogenic Cells (2015)
  • Author(s): Yazawa Ｔ，他5名
  • Journal Title: American Journal of Life Sciences Volume: 3 Issue: 3 Pages: 58-64
  • DOI: 10.11648/j.ajls.s.2015030302.21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Steroidogenesis, Development, and Cell Differentiation by Steroidogenic Factor-1 and Liver Receptor Homolog-1. (2015)
  • Author(s): Yazawa T, 他６名
  • Journal Title: Zoological Science Volume: 32 Issue: 4 Pages: 323-330
  • DOI: 10.2108/zs140237
  • NAID: 210000170450
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ｉntestinal Secretion and Barrier Function; Implication with Muscarinic Cholinoceptor (2015)
  • Author(s): Khan, MR, Yazawa T, 他３名
  • Journal Title: American Journal of Life Sciences Volume: 3 Issue: 4 Pages: 311-315
  • DOI: 10.11648/j.ajls.20150304.19
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of muscarinic cholinoceptor ameliorates tumor necrosis factor-a-induced barrier dysfunction in intestinal epithelial cells. (2015)
  • Author(s): Khan MR, Uwada J, Yazawa T, Islam MT, Krug SM, Fromm M, Karaki S, Suzuki Y, Kuwahara A, Yoshiki H, Sada K, Muramatsu I, Anisuzzaman AS and Taniguchi T.
  • Journal Title: FEBS Lett. Volume: 589 Issue: 23 Pages: 3640-3647
  • DOI: 10.1016/j.febslet.2015.10.029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 幹細胞からのステロイドホルモン産生細胞の分化誘導 (2017)
  • Author(s): 矢澤隆志、今道力敬、宮本薫、宇和田淳介、谷口隆信
  • Organizer: 第90回 日本内分泌学会学術総会
  • Invited
• [Presentation] ライディッヒ細胞におけるEP受容体を介したステロイドホルモン産生調節機構 (2017)
  • Author(s): 矢澤隆志、今道力敬、宮本薫、宇和田淳介、谷口隆信
  • Organizer: 第90回 日本内分泌学会学術総会
• [Presentation] 哺乳類における11-ケトテストステロン産生 (2017)
  • Author(s): 矢澤隆志、今道力敬、宮本薫、宇和田淳介、谷口隆信
  • Organizer: 第88回 日本動物学会富山大会
• [Presentation] ホルモンが農と食に及ぼした光と影 (2017)
  • Author(s): 矢澤隆志、佐藤貴弘
  • Organizer: ConBio 2017
  • Invited
• [Presentation] 幹細胞を用いたステロイドホルモン産生経路の解析 (2017)
  • Author(s): 矢澤隆志
  • Organizer: 第二回 性と生殖の懇談会
  • Invited
• [Presentation] DES投与が幼若ラット卵巣のステロイドホルモン産生に及ぼす影響 (2017)
  • Author(s): 矢澤隆志、今道力敬
  • Organizer: 日本動物学会北海道支部第６２回大会
• [Presentation] ヒトにおける11-ケトテストステロン産生とその機能 (2017)
  • Author(s): 矢澤隆志
  • Organizer: 第２１回日本生殖内分泌学会
  • Place of Presentation: 大阪
• [Presentation] Novel androgen metabolic pathway in human gonads (2016)
  • Author(s): Yazawa T, Imamichi Y, Uwada J, Taniguchi T
  • Organizer: 第２２回国際動物学会
  • Place of Presentation: Okinawa
  • Year and Date: 2016-11-14
  • Int'l Joint Research
• [Presentation] （原文）：精巣・ライディッヒ細胞におけるCox-2の発現とステロイドホルモン産生制御 (2016)
  • Author(s): 矢澤隆志、今道力敬、宇和田淳介、谷口隆信
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] （原文）：幹細胞からのステロイドホルモン産生細胞の分化誘導とホルモン産生機構の解明 (2016)
  • Author(s): 矢澤隆志
  • Organizer: 第８９回日本内分泌学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-21
  • Invited
• [Presentation] 幹細胞からのステロイドホルモン産生細胞の作製とホルモン産生機構の解明 (2016)
  • Author(s): 矢澤隆志
  • Organizer: 第6回長浜若手バイオセミナー
  • Place of Presentation: 長浜
  • Year and Date: 2016-02-26
• [Presentation] 生殖内分泌とステロイドホルモン産生 (2016)
  • Author(s): 矢澤隆志
  • Organizer: 第７回ペプチド・ホルモン研究会
  • Place of Presentation: 久留米
  • Invited
• [Presentation] ヒトにおける11-ケトテストステロンの産生とその役割 (2015)
  • Author(s): 今道力敬、矢澤隆志
  • Organizer: BMB2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Journal EditorとReviewerの話 (2015)
  • Author(s): 矢澤隆志、今道力敬
  • Organizer: 第6回ペプチド・ホルモン研究会
  • Place of Presentation: 能登
  • Year and Date: 2015-10-16
• [Presentation] ライディッヒ細胞におけるプロスタグランジン産生とその機能 (2015)
  • Author(s): 矢澤隆志、今道力敬、宮本薫、谷口隆信
  • Organizer: 日本動物学会第86回新潟大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-09-17
• [Presentation] TJ構成因子FAKは、ムスカリンM1受容体シグナルを介した腸上皮バリア機能維持や修復の標的となる (2015)
  • Author(s): 矢澤隆志、宇和田淳介、イスラムタリクル、谷口隆信
  • Organizer: 第112回北海道癌談話会例会
  • Place of Presentation: 札幌
  • Year and Date: 2015-09-12
• [Presentation] ヒト生殖腺での11-ケトテストステロンの産生と機能 (2015)
  • Author(s): 矢澤隆志、今道力敬
  • Organizer: 平成27年度日本動物学会北海道支部会
  • Place of Presentation: 札幌
  • Year and Date: 2015-08-22
• [Presentation] 幹細胞からのステロイドホルモン産生細胞の分化 (2015)
  • Author(s): 矢澤隆志
  • Organizer: 第1回帝京大学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2015-04-25
  • Invited
• [Presentation] ライディッヒ細胞におけるCox-2発現制御とプロスタグランジン産生 (2015)
  • Author(s): 矢澤隆志、今道力敬、宮本薫、谷口隆信
  • Organizer: 第８８回日本内分泌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23