Enhanced mitophagy in Sertoli cells of ethanol-treated rats: morphological evidence and clinical relevance |
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Authors: | Nabil Eid Yuko Ito Yoshinori Otsuki |
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Institution: | (1) Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki Osaka, 569-8686, Japan; |
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Abstract: | Although chronic ethanol consumption results in Sertoli cell vacuolization and augmented testicular germ cell apoptosis via
death receptor and mitochondrial pathways, Sertoli cells are resistant to apoptosis. The aim of this study was to examine
whether the activation of autophagy in the Sertoli cells of ethanol-treated rats (ETR) may have a role in their survival.
Adult Wistar rats were fed either 5% ethanol in Lieber–DeCarli liquid diet or an isocaloric control diet for 12 weeks. The
TUNEL method demonstrated that Sertoli cells were always TUNEL-negative despite the presence of many apoptotic germ cells
in ETR, supporting our previous studies. Electron microscopy revealed the presence of large numbers of autophagic vacuoles
(AVs) in Sertoli cells of ETR compared to few AVs in control testes. Most of the AVs in Sertoli cells of ETR enveloped and
sequestered damaged and abnormally shaped mitochondria, without cytoplasm, indicating mitochondrial autophagy (mitophagy).
Immuno-electron microscopy showed the localization of LC3, a specific marker of early AVs (autophagosomes), around AVs sequestering
mitochondria in Sertoli cells of ETR. Immunohistochemical staining of LC3 demonstrated a punctate pattern in Sertoli cells
of ETR, confirming the formation of autophagosomes, while LC3 puncta were almost absent in control testes. Moreover, increased
immunoreactivity of LAMP-2, a lysosomal membrane protein and marker of late AVs (autolysosomes), was mainly observed in Sertoli
cells of ETR, with weaker expression in control testes. Via the deletion of pro-apoptotic damaged mitochondria, enhanced Sertoli
cell mitophagy in ETR may be an anti-apoptotic mechanism that is essential for spermatogenesis. |
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