Sperm maturation induced by immunocompetent cells and symbiotic bacteria

• Project/Area Number: 15K21098
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology; Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Watanabe Hitomi 京都大学, ウイルス・再生医科学研究所, 助教 (80624056)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 精子 / Lipocalin2 / 免疫担当細胞 / 常在細菌叢 / 性ホルモン制御 / 精子活性化 / 子宮粘膜 / RAG2依存性免疫細胞 / インヒビン / 卵巣腫瘍 / 卵巣由来分泌因子 / Ｌｃｎ２ / 免疫細胞 / 生殖ホルモン / Lcn2 / 受精メカニズム / 精子成熟化シグナル

Outline of Final Research Achievements

In this study, the mechanism of expression control of Lipocalin 2 (Lcn 2), a sperm maturation factor derived from uterine mucosa, was elucidated, thereby clarifying the fertilization control mechanism caused by the microenvironment of reproductive mucosa, and establishing the method of diagnosis and treatment of infertility. As a result of the study, the sex hormone control system in the pituitary - ovary axis leads to the periodicity of Lcn2 expression from uterine mucosa, but its constitutive expression is mediated by the presence of RAG2 - dependent immune cells and resident flora.

Research Products

• [Journal Article] Stem cell nich-specific Ebf3 maintains the bone marrow cavity. (2018)
  • Author(s): Seike, M., Omatsu, Y., Watanabe, H., Kondoh, G., Nagasawa, T.
  • Journal Title: Genes & Development Volume: 32 Pages: 359-372
  • DOI: 10.1101/gad.311068.117
  • Peer Reviewed / Open Access
• [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth. (2018)
  • Author(s): M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
  • Journal Title: Cancer Cell Volume: 12 Pages: 355-367
  • DOI: 10.1016/j.ccell.2018.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes. (2018)
  • Author(s): Shukunami C, Takimoto A, Nishizaki Y, Yoshimoto Y, Tanaka S, Miura S, Watanabe H, Sakuma T, Yamamoto T, Kondoh G, Hiraki Y.
  • Journal Title: Sci Rep Volume: 8 Pages: 1-12
  • DOI: 10.1038/s41598-018-21194-3
  • NAID: 120006522882
  • Peer Reviewed / Open Access
• [Journal Article] Novel adherent CD11b+ Gr-1+ tumor-infiltrating cells initiate an immunosuppressive tumor microenvironment. (2018)
  • Author(s): Tsubaki T, Kadonosono T, Sakurai S, Shiozawa T, Goto T, Sakai S, Kuchimaru T, Sakamoto T, Watanabe H, Kondoh G, Shinae Kizaka-Kondoh.
  • Journal Title: Oncotarget Volume: 9 Pages: 11209-11226
  • DOI: 10.18632/oncotarget.24359
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disruption of circadian clockwork in in vivo reprogramming-induced mouse kidney tumors (2018)
  • Author(s): Ohashi Munehiro、Umemura Yasuhiro、Koike Nobuya、Tsuchiya Yoshiki、Inada Yutaka、Watanabe Hitomi、Tanaka Tomoko、Minami Yoichi、Ukimura Osamu、Miki Tsuneharu、Tajiri Tatsuro、Kondoh Gen、Yamada Yasuhiro、Yagita Kazuhiro
  • Journal Title: Genes Cells Volume: 23 Pages: 60-69
  • DOI: 10.1111/gtc.12552
  • Peer Reviewed / Open Access
• [Journal Article] Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice. (2017)
  • Author(s): Hara H, Miyata H, Das NR, Chida J, Yoshimochi T, Uchiyama K, Watanabe H, Kondoh G, Yokoyama T, Sakaguchi S
  • Journal Title: Journal of Virology Volume: -
  • DOI: 10.1128/jvi.01368-17
  • Peer Reviewed / Open Access
• [Journal Article] PARI regulates stalled replication fork proessing to maintain genome stability upon replication stress in mice (2017)
  • Author(s): Ayako L. Mochizuki, Ami Katanaya, Eri Hayashi, Mihoko Hosokawa, Emiko Moribe, Akira Motegi, Masamichi Ishiai,Minoru Takata, Gen Kondoh, Hitomi Watanabe, Norio Nakatsuji, and Shinichiro Chuma
  • Journal Title: Mol Cell Biol. Volume: 37 (23)
  • DOI: 10.1128/mcb.00117-17
  • Peer Reviewed / Open Access
• [Journal Article] Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system. (2017)
  • Author(s): Yoshimoto Y, Takimoto A, Watanabe H, Hiraki Y, Kondoh G, Shukunami C.
  • Journal Title: Scientific Reports Volume: 7 Pages: 45010-45010
  • DOI: 10.1038/srep45010
  • NAID: 120005998026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of prion protein devoid of the N-terminal residues 25-50 on prion pathogenesis in mice. (2017)
  • Author(s): Nandita Rani Das, Hironori Miyata, Hideyuki Hara, Keiji Uchiyama, Junji Chida, Masashi Yano, Hitomi Watanabe, Gen Kondoh, Suehiro Sakaguchi
  • Journal Title: Arc. Virol. Volume: 印刷中 Pages: 1867-1876
  • DOI: 10.1007/s00705-017-3295-3
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lipid raft dynamics linked to sperm competency for fertilization in mice. (2017)
  • Author(s): Watanabe, H., R. Takeda, K. Hirota, G. Kondoh.
  • Journal Title: Genes to Cells Volume: 印刷中
  • DOI: 10.1111/gtc.12491
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse. (2015)
  • Author(s): Tsuchiya Y., Minami Y., Umemura Y., Watanabe H., Ono D., Nakamura W., Takahashi T., Honma S., Kondoh G., Matsuishi T. & Yagita K.
  • Journal Title: Genes Cells Volume: 20 Pages: 992-1005
  • DOI: 10.1111/gtc.12305
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] マウス精子受精能とラフト局在変化の相関性 (2018)
  • Author(s): 渡邉仁美、竹田理恵、廣田圭司、近藤玄
  • Organizer: 第65回日本実験動物学会総会
• [Presentation] Lipid raft dynamics linked to sperm competency for fertilization in mice (2017)
  • Author(s): Gen Kondoh, Hitomi Watanabe, Rie Takeda and Keiji Hirota
  • Organizer: 第4回国際生殖生物学会
  • Int'l Joint Research
• [Presentation] Development and characterization of monoclonal antibodies against a stable sperm surface antigen. (2016)
  • Author(s): Hitomi Watanabe, Takatoku Oida, Gen Kondoh and Keiji Hirota
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 那覇市
  • Year and Date: 2016-12-05
• [Presentation] マウス精子成熟における遺伝的背景の影響について (2016)
  • Author(s): 渡邊 仁美、竹田 理恵、廣田 圭司、近藤 玄
  • Organizer: 第63回日本実験動物学会総会
  • Place of Presentation: 川崎市
  • Year and Date: 2016-05-05
• [Presentation] マウス精子成熟における遺伝的背景の影響について (2016)
  • Author(s): 渡邊 仁美
  • Organizer: 京都大学再生医科学研究所 若手発表会
  • Place of Presentation: 京都
  • Year and Date: 2016-01-21