Autophagy is required for ectoplasmic specialization assembly in sertoli cells

Abstract

The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, PDLIM1, and these defects could be partially rescued by Pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of PDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.

miR‐26a suppresses autophagy in swine Sertoli cells by targeting ULK2

“…However, Sertoli cells also provide the nutrients and regulatory factors for supporting all phases of germ cell development and maturity when they lose their proliferative ability in mature testis (Chojnacka, Zarzycka, & Mruk, ; Dimitriadis et al., ; Gerber, Heinrich, & Brehm, ). Accumulating evidence has shown that autophagy can guarantee the normal functional role to support germ cell development and maturity through degradation of the PDLIM1 protein or degradation of ingested cell‐derived substrates (Liu et al., ; Yefimova et al., ). Based on these above‐mentioned clues, we aimed to investigate the regulation mechanisms of miR‐26a in swine Sertoli cell autophagy in this study.…”

Contribution of Autophagy to the Physiological and Pathophysiological Functions in the Mammalian Testis

“…Unwanted distribution of TBCs directly impaired the function of Sertoli cells as well as the communication between Sertoli cells and germ cells. Liu et al suggested that the different influences of autophagy on apical ES and TBCs assembly might come from their different F-actin arrangements, because F-actin is packed in hexagonal arrays in the ES, while it appears as an embranchment surrounding the tubular portion of TBCs [36,58,59]. Furthermore, the incorrect distribution of TBCs might also be resulted from the abnormal structure of apical ES or the malformation of sperm head, whereas these possibilities still remain to be uncovered by further experimental data.…”

“…Successful organization of cytoskeleton in Sertoli cell is highly related to the produce of functional spermatozoa. The accumulation of PDLIM1 disrupts the F-actin hoops of the apical ES and related microtubule-based structures in the seminiferous epithelium, which ultimately leading to the disruption of Sertoli cell-germ cell communication thereafter contributing to the malformation of sperm head [36].…”

“…In essence, the functions of Sertoli cells are related to its paralleled structural basis, the malformation of cellular structure frequently leads to the infertility of male. Autophagy plays pivotal roles in the regulation of Sertoli cell functions via cytoskeleton adjustment [36].…”

Mechanistic insights into acephalic spermatozoa syndrome–associated mutations in the human SUN5 gene

“…The immunofluorescence and immunohistochemical assays were performed as previously described (19). For IF staining of human sperm, semen was spread on polylysine-coated slides and dried in air, then fixed with 4% PFA and stained with FITC-PNA for acrosomes and DAPI for DNA.…”