1. Wnt5a Regulates Junctional Function of Sertoli cells Through PCP-mediated Effects on mTORC1 and mTORC2.
- Author
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Fu Y, Wei Y, Zhou Y, Wu H, Hong Y, Long C, Wang J, Wu Y, Wu S, Shen L, and Wei G
- Subjects
- Actin Cytoskeleton metabolism, Animals, Blood-Testis Barrier, Gene Expression Profiling, Germ Cells cytology, Ligands, Male, Microfilament Proteins metabolism, Phagosomes, RNA, Small Interfering metabolism, Rats, Rats, Sprague-Dawley, Seminiferous Epithelium metabolism, Signal Transduction, Spermatids metabolism, Spermatogenesis genetics, Testis metabolism, Wnt-5a Protein metabolism, Gene Expression Regulation, Mechanistic Target of Rapamycin Complex 1 biosynthesis, Mechanistic Target of Rapamycin Complex 2 biosynthesis, Sertoli Cells metabolism, Wnt-5a Protein biosynthesis
- Abstract
The blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells, and then identified elongated spermatids that lost their polarity and were embedded in the seminiferous epithelium. Moreover, phagosomes were found near the tubule lumen. These defects were due to BTB and apical ES disruption. We also verified that the expression level and/or location of BTB-associated proteins, actin binding proteins (ABPs), and F-actin was changed after Wnt5a knockdown in vivo and in vitro. Additionally, we demonstrated that Wnt5a regulated actin dynamics through Ror2-mediated mTORC1 and mTORC2. This study clarified the molecular mechanism of Wnt5a in Sertoli cell junctions through the planar cell polarity (PCP) signaling pathway. Our findings could provide an experimental basis for the clinical diagnosis and treatment of male infertility caused by Sertoli cell junction impairment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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