Elucidation of pathogenesis of male infertility and search for new treatment focusing on anti-aging gene SIRT1

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09671
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kochi University (2022); Tottori University (2019-2021)
• Principal Investigator: Nakane Hironobu 高知大学, 教育研究部医療学系基礎医学部門, 教授 (10304205)
• Co-Investigator(Kenkyū-buntansha): 小山 友香 鳥取大学, 医学部, 助教 (30827572)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: DNA修復欠損マウス / Xpaマウス / sirt1 / 精子形成不全 / autophagy

Outline of Final Research Achievements

There is a need for a new, less invasive treatment for male infertility. The purpose of this study is to develop a treatment method based on the new pathology of spermatogenic dysfunction, as DNA repair defects have been reported in some cases of male infertility. In this study, we found that testicular degeneration in DNA repair-deficient mice (Xpa mice) is due to the induction of autophagy, which we published in a paper (Nakane et al, 2020). In addition, autophagy monitor DNA repair-deficient mice (Xpa-LC3) develop testicular lesions earlier than Xpa mice, revealing the possibility of assessing the effects of NAD+ intermediates. Furthermore, using these mice, comprehensive analysis of Xpa-LC3 mouse testis by NAD+ intermediates is underway.

Free Research Field

解剖学、男性不妊症

Academic Significance and Societal Importance of the Research Achievements

我々は、DNA修復を欠き老化促進を示すXpaマウスを用いたので、抗老化因子の低下によるオートファジーの亢進が見いだせた。本研究の「 造精障害を老化促進ととらえた」着想は、この系の独自性に導かれ他に例を見ない。本研究で使用するNAD+中間体は内在性生理物質で、生体内で常に使用されていて次世代の遺伝情報への影響はないと考えられ安全である(ヒトでも確認)。本研究は、他の造精障害の治療法[再生医療・ 遺伝子導入]と異なり、不妊患者本人の精巣内環境の破綻状態を改善し、造精可能な環境を整え精子形成を維持する治療である。この治療の有用性が示せれば、インパクトは大きいであろう。