Elucidation of somatic testicular cell abnormalities in male infertility and their application to new gene therapy

• Project/Area Number: 18K16706
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Nagoya City University
• Principal Investigator: NOZAKI SATOSHI 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (50813432)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ライディッヒ細胞 / ホルモン異常 / 精巣毒性 / 男性不妊症 / 間質浮腫 / 男性不妊動物モデル / Setoli細胞 / Leydig細胞 / 無精子症 / Sertoli細胞 / 遺伝子導入

Outline of Final Research Achievements

Advances in assisted reproductive technology in male infertility have made remarkable progress, and surgery to collect intratesticular sperm under a microscope has become the standard treatment. However, sperm are not found in more than half, and it is necessary to establish a new treatment method. Therefore, we focused on testicular somatic cells rather than germ cells. As a result, we succeeded in isolating Leydig cells and clarified the mechanism of sperm dysfunction in hormonally abnormal male infertility model animals.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、精巣の体細胞であるライディッヒ細胞を効率よく分離することに成功した。また、LH-RH製剤を投与したホルモン異常男性不妊症モデル動物において、精巣間質の拡大とIL-6分泌の増加を明らかにした。今後、精巣間質の主体であるライディッヒ細胞をターゲットとする治療を行うことにより、次世代に伝播しない遺伝子治療が可能になると考える。

Research Products

• [Journal Article] Efficacy of fosfomycin in the prevention of postoperative infection following transurethral resection of bladder tumor during periods of limited cefazolin, cefotiam, and cefmetazole supply (2021)
  • Author(s): Etani Toshiki、Asaoka Minami、Kondo Shuhei、Wachino Chiharu、Hori Kaoru、Shimizu Nobuhiko、Noda Yusuke、Nagai Takashi、Nozaki Satoshi、Iida Keitaro、Naiki Taku、Ando Ryosuke、Kawai Noriyasu、Yanagita Takeshi、Nakamura Atsushi、Yasui Takahiro
  • Journal Title: Journal of Infection and Chemotherapy Volume: 27 Issue: 4 Pages: 625-631
  • DOI: 10.1016/j.jiac.2020.11.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Selective lysine-specific demethylase 1 inhibitor, NCL1, could cause testicular toxicity via the regulation of apoptosis (2020)
  • Author(s): Nozaki S, Naiki T, Naiki-Ito A, Iwatsuki S, Takeda T, Etani T, Nagai T, Iida K, Kato H, Suzuki T, Takahashi S, Umemoto Y, Yasui T.
  • Journal Title: Andrology Volume: 8 Issue: 6 Pages: 1895-1906
  • DOI: 10.1111/andr.12846
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Selective lysine specific demethylase 1 inhibitor, NCL1, could cause testicular toxicity via the regulation of apoptosis (2020)
  • Author(s): Nozaki Satoshi, Naiki Taku, Iwatsuki Shoichiro, Naiki-Ito Aya, Takeda Tomoki, Etani Toshiki, Kurokawa Satoshi, Takahashi Satoru, Umemoto Yukihiro, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2020(web開催)
  • Int'l Joint Research
• [Presentation] LHシグナルは精巣の間質浮腫に関与する (2020)
  • Author(s): 野崎 哲史、岩月 正一郎、武田 知樹、窪田 裕樹、窪田 泰江、佐々木 昌一、梅本 幸裕、安井 孝周
  • Organizer: 第65回日本生殖医学会学術講演会・総会
• [Presentation] Isolation of testicular somatic cells using DSA lectin and Percoll (2018)
  • Author(s): Satoshi Nozaki, Shoichiro Iwatsuki, Tomoki Takeda, Hiroki Kubota, Hiroyuki Kamiya, Shoichi Sasaki, Yukihiro Umemoto, Takahiro Yasui
  • Organizer: 第106回 日本泌尿器科学会総会