Inhibition of ImiR-143-3p/I Restores Blood–Testis Barrier Function and Ameliorates Sertoli Cell Senescence

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 4
• Main Authors: Xiao, Ziyan, Liang, Jinlian, Huang, Rufei, Chen, Derong, Mei, Jiaxin, Deng, Jingxian, Wang, Zhaoyang, Li, Lu, Li, Ziyi, Xia, Huan, Yang, Yan, Huang, Yadong
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.02.2024
• Subjects: Age factors in disease; Aging; Analysis; Cells; Medical examination; MicroRNA; Reproductive organs, Male; China
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13040313

Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation of miR-143-3p expression. miR-143-3p was found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood–testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulating miR-143-3p. These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges.