Identification and functional analysis of Kansl1-L gene isoform in testis that controls sperm aging

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K09723
• 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: Kansai University of Health Sciences
• Principal Investigator: Hatamura Ikuji 関西医療大学, 保健医療学部, 教授 (80336883)
• Co-Investigator(Kenkyū-buntansha): 伊藤 俊治 関西医療大学, 保健医療学部, 教授 (50275351)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 精子形成 / Kansl1ーL遺伝子

Outline of Final Research Achievements

Kansl1-L KO mice were generated, and the testis of the KO mice was significantly smaller and had no spermatozoa compared to that of wild mice. The testis of the KO mice had no spermatogenesis compared to that of the wild mice. To analyze the mechanism of spermatogenesis, we performed DNA microanalysis of testis from KO and wild mice and found significant differences in aging-related gene groups. We have also analyzed the Kansl1-L gene and aging-related genes (Sirt1, klotho, etc.) in spermatocytes and found that these genes act during the first wave of spermatogenesis. This suppression of Ccna1 expression may result in cell division retardation, induction of apoptosis, and cell differentiation arrest of spermatogenesis. It is also thought that reduced Klotho gene expression in testis failed to suppress sperm cell senescence and promoted spermatocyte apoptosis. The Kansl1-L gene is thought to be an important regulator of the early differentiation of spermatogenesis.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

近年の日本では不妊治療の件数が増加してきており、とくに男性不妊が以前と比べ急激に増加傾向である。その原因の一つに精子の産生能の低下や、晩婚による精子の加齢が挙げられている。本研究において精子形成の初期にKansl1-L遺伝子が重要な役割を担っており、この遺伝子が欠損することにより、精子の細胞分化が停止し、さらには加齢遺伝子に影響を及ぼし、精子形成の初期の分化を制御していると考えられた。男性不妊の一端である精子低形成に及ぼす可能性があり、この遺伝子を活性化することにより、男性不妊の改善に寄与できると考えられた。