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

Authors :
Ziyan Xiao
Jinlian Liang
Rufei Huang
Derong Chen
Jiaxin Mei
Jingxian Deng
Zhaoyang Wang
Lu Li
Ziyi Li
Huan Xia
Yan Yang
Yadong Huang
Source :
Cells, Vol 13, Iss 4, p 313 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

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.

Details

Language :
English
ISSN :
20734409
Volume :
13
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.b7e193ed16e4418875d710e14c4b7a3
Document Type :
article
Full Text :
https://doi.org/10.3390/cells13040313