The role of Sertoli cell-derived miR-143-3p in male fertility declines with age

• 主要な著者: Jinlian Liang (著者), Jiaxin Mei (著者), Derong Chen (著者), Ziyan Xiao (著者), Meirong Hu (著者), Siying Wei (著者), Zhaoyang Wang (著者), Rufei Huang (著者), Lu Li (著者), Tao Ye (著者), Jingxian Deng (著者), Yuan Liu (著者), Yuxin Wang (著者), Lei Zhang (著者), Yan Yang (著者), Yadong Huang (著者)
• フォーマット: 図書
• 出版事項: Elsevier, 2024-12-01T00:00:00Z.
• 主題: article
• オンライン･アクセス: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2024.102369
• Keywords: MT: Non-coding RNAs; miR-143-3p; extracellular vesicles; EVs; Sertoli cells; male fertility; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 35, Iss 4, Pp 102369- (2024)

As delayed parenthood becomes more prevalent, understanding age-related testosterone decline and its impact on male fertility has gained importance. However, molecular mechanisms concerning testicular aging remain largely undiscovered. Our study highlights that miR-143-3p, present in aging Sertoli cells (SCs), is loaded into extracellular vesicles (EVs), affecting Leydig cells (LCs) and germ cells, thus disrupting testicular tissue homeostasis and spermatogenesis. Intriguingly, in SCs, transforming growth factor-β signaling promotes miR-143 precursors transcription, increasing mature miR-143-3p levels. This inhibits Smurf2, activating Smad2, and further enhancing miR-143-3p accumulation. EVs transporting miR-143-3p, originating from SCs, contribute to the age-related decline of testosterone and male fertility by targeting the luteinizing hormone receptor and retinoic acid receptor. Diminishing endogenous miR-143-3p in SCs postpones testis aging, preserving and prolonging male fertility. Thus, our study identified miR-143-3p as a key regulator of testicular function and fertility, revealing miR-143-3p as a potential therapeutic target for male abnormal sexual and reproductive function.