Establishment of a new therapeutic platform for male infertility based on a complete picture of testis-specific metabolic states.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03067
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka University
• Principal Investigator: FUKUHARA Shinichiro 大阪大学, 大学院医学系研究科, 准教授 (20609870)
• Co-Investigator(Kenkyū-buntansha): 竹澤 健太郎 大阪大学, 大学院医学系研究科, 助教 (90648015) ; 木内 寛 大阪大学, 大学院医学系研究科, 招へい教員 (70403053)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 精巣 / クレアチン / 男性不妊

Outline of Final Research Achievements

The causes of male infertility are still largely unknown. Creatine is stored in the body as an energy buffer, and the testes are the second most abundant organ after muscle. Furthermore, creatine in the testes has long been known to be decreased in male infertile patients, but its role is unknown. In this study, we investigated the role of creatine in the testis, focusing on creatine synthesizing enzyme Gamt and creatine transporter Slc6a8. Slc6a8 knockout mice showed no abnormalities in spermatogenesis. On the other hand, Gamt knockout mice formed spermatozoa but had a reduced sperm count and decreased sperm motility. In addition, creatine in the testes of Gamt knockout mice was significantly decreased, resulting in disruption of tight junction, and creatine supplementation in Gamt knockout mice improved sperm count. In conclusion, we identified creatine as being required for the maintenance of the tight junction in the testis.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、GamtおよびSlac6a8ノックアウトが精巣のクレアチンレベルに及ぼす影響を調べることにより、本研究は、クレアチンが男性の生殖生物学に関与するというこれまで未解明であった側面を明らかにした。
さらにクレアチンが精巣のタイトジャンクションの維持に必要であること、そしてクレアチンの欠乏を改善することでこの機能を回復できることを見出した。クレアチンは、病態生理学に基づいた治療法のない男性不妊症治療の分野において、新たな治療標的となりうると考えられる。