The regulation of FSHR expression during folliculogenesis

• Project/Area Number: 18K16767
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya University
• Principal Investigator: Nakamura Tomoko 名古屋大学, 医学部附属病院, 講師 (40732681)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵胞発育 / FSHレセプター / BMP15 / phoenixin / 卵胞刺激ホルモン受容体 / 顆粒膜細胞 / FSHR / エピジェネティック / パラクライン因子

Outline of Final Research Achievements

Our study elucidated the effects of Bone Morphogenetic Protein 15 (BMP15) and the novel neuropeptide phoenixin which induces follicle stimulating hormone receptor (FSHR) expression in　human granulosa cells. BMP15 elevates FSHR expression in human granulosa cells by epigenetically modifying the promoter region of the FSHR gene through both Smad and non-Smad pathways. Phoenixin accelerates granulosa cell proliferation and increases steroid production as well as inducing FSHR expression. Murine ovarian tissue culture showed that phoenixin stimulates follicle growth and increases ovulation, thereby describing the role of phoenixin in the ovary.

Academic Significance and Societal Importance of the Research Achievements

顆粒膜細胞がFSHRを適切に発現することは良質な卵を得るために必須である。卵胞顆粒膜細胞におけるFSHR発現制御機構の解明は、妊孕性の高い良質な卵を多く獲得するための知見を与え、卵胞発育刺激に対するpoor responderへの補助療法開発に役立つ可能性がある。また近年、悪性腫瘍治療前の女性の卵巣凍結による妊孕性温存が臨床応用されているが、癌治療後の自家移植時に、移植組織片に混じった癌細胞をも移植してしまうリスクがある。これはヒト卵胞の完全体外培養系による成熟卵の獲得により解決されうるが、FSHR発現制御機構の解明はこの点にも寄与すると期待される。

Research Products

• [Journal Article] Molecular mechanism of FSHR expression induced by BMP15 in human granulosa cells (2019)
  • Author(s): Shimizu Ken、Nakamura Tomoko、Bayasula、Nakanishi Natsuki、Kasahara Yukiyo、Nagai Takashi、Murase Tomohiko、Osuka Satoko、Goto Maki、Iwase Akira、Kikkawa Fumitaka
  • Journal Title: Journal of Assisted Reproduction and Genetics Volume: 36 Issue: 6 Pages: 1185-1194
  • DOI: 10.1007/s10815-019-01469-y
  • Peer Reviewed
• [Journal Article] Effect of the Neuropeptide Phoenixin and Its Receptor GPR173 During Folliculogenesis (2019)
  • Author(s): Nguyen Xuan Phuoc、Nakamura Tomoko、Osuka Satoko、Bayasula Bayasula、Nakanishi Natsuki、Kasahara Yukiyo、Muraoka Ayako、Hayashi Shotaro、Nagai Takashi、Murase Tomohiko、Goto Maki、Iwase Akira、Kikkawa Fumitaka
  • Journal Title: Reproduction Volume: Epub Issue: 1 Pages: 25-34
  • DOI: 10.1530/rep-19-0025
  • Peer Reviewed
• [Presentation] Suppression of gonadotropin sensitivity and steroidogenesis in human granulosa cells by endometriotic stroma cells (2019)
  • Author(s): Hayashi S, Nakamura T, Murakami M, Miyake N, Muraoka A, Kasahara Y, Nakanishi N, Nagai T, Murase T, Osuka S, Goto M, KIkkawa F
  • Organizer: 第71回日本産科婦人科学会学術講演会
• [Presentation] Expressions and Effects of Phoenixin and Its Receptor GPR173 During the Human Menstrual Cycle (2019)
  • Author(s): Xuan Phuoc Nguyen, Nakamrura T, Osuka S, Bayasula, Muraoka A, Hayashi S, Nakanishi N, Kasahara Y, Murase T, Goto M, Iwase A, Kikkawa F
  • Organizer: 67th Society for Reproductive Investigation Annual Scientific Meeting
  • Int'l Joint Research
• [Presentation] BMP15 がFSHRを誘導する機序の解明 (2018)
  • Author(s): 清水顕、岩瀬明、吉田沙矢子、村岡彩子、林祥太郎、仲西菜月、永井孝、邨瀬智彦、大須賀智子、中村智子、後藤真紀、吉川史隆
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] The effect of neuropeptide Phoenixin on folliculogenesis (2018)
  • Author(s): Xuan Phuoc Nguyen, Tomoko Nakamura, Shotaro Hayashi, Ayako Muraoka, Natsuki Nakanishi, Yukiyo Kasahara, Takashi Nagai, Tomohiko Murase, Satoko Osuka, Maki Goto, Akira Iwase, Fumitaka Kikkawa
  • Organizer: 第63回日本生殖医学会学術講演会
• [Presentation] Directive Action of Neuropeptide Phoenixin and Its Receptor GPR173 During Folliculogenesis (2018)
  • Author(s): Xuan Phuoc Nguyen, Akira Iwase, Tomohiko Murase, Umida Ganieva, Ying Qin, Bayasula, Ken Shimizu, Satoko Osuka, Tomoko Nakamura, Maki Goto, Fumitaka Kikkawa
  • Organizer: Society for Reproductive Investigation 65th Annual Scientific Meeting
  • Int'l Joint Research
• [Presentation] Neuropeptide phoenixin (PNX) and its novel receptor GPR173 induce COX-1/COX-2 expression and PGE2 production through CREB signaling pathway (2018)
  • Author(s): Xuan Phuoc Nguyen, Tomoko Nakamura, Tomohiko Murase, Umida Ganieva, Ying Qin, Bayasula, Ken Shimizu, Satoko Osuka, Maki Goto, Akira Iwase, Fumitaka Kikkawa
  • Organizer: European Society of Human Reproduction and Embryology 34th Annual Meeting
  • Int'l Joint Research