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

• DOI: 10.1007/s00018-022-04521-w
• Publication Date: 2022-08-25T19:02:46Z
• Authors: Yue Feng; Dake Chen; Tiansu Wang; Jiawei Zhou; Wenning Xu; Hao Xiong; Rong Bai; Shang Wu; Jialian Li; Fenge Li
• Keywords: Male; Mammals; 0301 basic medicine; 0303 health sciences; Sertoli Cells; Cell Survival; Swine; Actins; Rats; Tight Junctions; Rats, Sprague-Dawley; Mice; MicroRNAs; 03 medical and health sciences; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Animals; Original Article; Spermatogenesis; Microtubule-Associated Proteins

AbstractSertoli 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.