4.7 Article

Zearalenone Induces Apoptosis and Autophagy in a Spermatogonia Cell Line

Journal

TOXINS
Volume 14, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/toxins14020148

Keywords

zearalenone; GC-1 spg cells; reproductive toxicity; apoptosis; autophagy

Funding

  1. National Research Foundation of Korea (NRF) - Korean government (MIST) [2021R1G1A1091690]
  2. National Research Foundation of Korea [2021R1G1A1091690] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study evaluated the molecular mechanisms of toxicity and cell damage induced by ZEN in GC-1 spermatogonia cells. The results showed that ZEN decreased cell viability and increased apoptosis in a dose-dependent manner. Moreover, ZEN also triggered autophagy in these cells. These findings reveal the toxic effects of ZEN on GC-1 spermatogonia cells and provide insights into its molecular mechanisms.
Zearalenone (ZEN), a widely known mycotoxin, is mainly produced by various Fusarium species, and it is a potent estrogenic metabolite that affects reproductive health in livestock and humans. In this study, the molecular mechanisms of toxicity and cell damage induced by ZEN in GC-1 spermatogonia (spg) cells were evaluated. Our results showed that cell viability decreased and apoptosis increased in a dose-dependent manner when GC-1 spg cells were exposed to ZEN. In addition, the key proteins involved in apoptosis, cleaved caspase-3 and -8, BAD, BAX, and phosphorylation of p53 and ERK1/2, were significantly increased in ZEN-exposed GC-1 spg cells for 24 h, and cytochrome c was released from mitochondria by ZEN. Interestingly, ZEN also triggered autophagy in GC-1 spg cells. The expression levels of the autophagy-related genes Atg5, Atg3, Beclin 1, LC3, Ulk1, Bnip 3, and p62 were significantly higher in ZEN-treated GC-1 spg cells, and the protein levels of both LC3A/B and Atg12 were remarkably increased in a dose-dependent manner in ZEN-exposed GC-1 spg cells compared to the control. In addition, immunostaining results showed that ZEN-treated groups showed a remarkable increase in LC 3A/B positive puncta as compared to the control in a dose-dependent manner based on confocal microscopy analysis in GC-1 spg cells. Our findings suggest that ZEN has toxic effects on tGC-1 spg cells and induces both apoptosis and autophagy.

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