Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis

• Published in: Cellular and molecular life sciences : CMLS 2022-09, Vol.79 (9), p.498-498, Article 498
• Main Authors: Feng, Yue, Chen, Dake, Wang, Tiansu, Zhou, Jiawei, Xu, Wenning, Xiong, Hao, Bai, Rong, Wu, Shang, Li, Jialian, Li, Fenge
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Actin; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cdc42 protein; Cell Biology; Cell proliferation; Cell survival; cell viability; Cofilin; genes; guanosinetriphosphatase; Lentivirus; Life Sciences; LIM kinase; Mammals; mice; microRNA; MicroRNAs; miRNA; Original; Original Article; Perturbation; Platelet-activating factor; Platelet-activating factor acetylhydrolase; Post-transcription; Proteins; Regulatory sequences; Sertoli cells; Spermatogenesis; Survival; Testes
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-022-04521-w

Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell–cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 ( Pafah1b1 ) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d- Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.