Effects of AGE-inhibitory DNA aptamer on male infertility

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06582
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Showa University
• Principal Investigator: Mori Yusaku 昭和大学, 医学部, 准教授 (90595919)
• Co-Investigator(Kenkyū-buntansha): 広村 宗範 昭和大学, 医学部, 兼任講師 (00773186) ; 山岸 昌一 昭和大学, 医学部, 教授 (40281026)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 終末糖化産物 / 男性不妊 / 糖尿病 / DNAアプタマー

Outline of Final Research Achievements

Although type 2 diabetes (T2DM) can be associated with sperm abnormality in male, the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules of diabetic complications. Here, we investigated the effects of AGE-inhibitory DNA aptamer (AGE-Apt) on the testes and spermatozoa in a mouse model of T2DM.
We found that AGEs were accumulated in the testes of diabetic mice, which were accompanied with testicular inflammation and impaired sperm quality and quantity. The administration of AGE-inhibitory DNA aptamer attenuated all of these changes. Our findings suggest that AGEs may cause sperm abnormality via testicular inflammation, and AGEs-Apt may be a potential therapeutic option against sperm abnormality in men with T2DM.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

未曾有の少子高齢化社会を迎えつつある我が国において、増加し続けている不妊症への対策は喫緊に取り組まなければならない課題の一つといえる。不妊症の約半数は男性に起因しており、生活・食習慣の欧米化やそれに伴う生活習慣病の蔓延が、男性不妊症のリスクになりうることが示唆されてきているが、その分子基盤は不明であった。本研究により、AGEsは男性不妊症と生活習慣病をつなぐ共通の分子標的であることが明らかにされ、DNAアプタマーという新たな治療手段が提示されることになり、その学問的かつ臨床的意義と価値は極めて大きい。