4.7 Article

Zearalenone Exposure Disrupts Blood-Testis Barrier Integrity through Excessive Ca2+-Mediated Autophagy

期刊

TOXINS
卷 13, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/toxins13120875

关键词

zearalenone; TM4 cells; blood-testis barrier; Ca2+; autophagy

资金

  1. National Key Research and Development Program of China [2016YFD0501208]
  2. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
  3. ordinary university graduate student scientific research innovation projects in Jiangsu province [KYCX20-2991]
  4. China Postdoctoral Science Foundation [2019M661952]

向作者/读者索取更多资源

The study demonstrated that exposure to Zearalenone (ZEA) resulted in severe testicular damage and a decrease in the expression of blood-testis barrier (BTB) junction-related proteins in a time-dependent manner, accompanied by an increase in autophagy-related proteins. In vitro, ZEA treatment led to an increase in cytoplasmic Ca2+ levels, autophagy markers LC3-II and p62 levels, and a decrease in BTB junction proteins, with the dislocation of the gap junction protein Cx43. Inhibition of autophagy or cytoplasmic Ca2+ was able to mitigate the effects of ZEA on BTB in TM4 cells.
Zearalenone (ZEA), a common mycotoxin in grains and animal feeds, has been associated with male reproductive disorders. However, the potential toxicity mechanism of ZEA is not fully understood. In this study, in vivo and in vitro models were used to explore the effects of ZEA on the blood-testis barrier (BTB) and related molecular mechanisms. First, male BALB/C mice were administered ZEA orally (40 mg/kg center dot bw) for 5-7 d. Sperm motility, testicular morphology, and expressions of BTB junction proteins and autophagy-related proteins were evaluated. In addition, TM4 cells (mouse Sertoli cells line) were used to delineate the molecular mechanisms that mediate the effects of ZEA on BTB. Our results demonstrated that ZEA exposure induced severe testicular damage in histomorphology and an ultrastructural, time-dependent decrease in the expression of blood-testis barrier junction-related proteins, accompanied by an increase in the expression of autophagy-related proteins. Additionally, similar to the in vitro results, the dose-dependent treatment of ZEA increased the level of cytoplasmic Ca2+ and the levels of the autophagy markers LC3-II and p62, in conjunction with a decrease in the BTB junction proteins occludin, claudin-11, and Cx43, with the dislocation of the gap junction protein Cx43. Meanwhile, inhibition of autophagy by CQ and 3-MA or inhibition of cytoplasmic Ca2+ by BAPTA-AM was sufficient to reduce the effects of ZEA on the TM4 cell BTB. To summarize, this study emphasizes the role of Ca2+-mediated autophagy in ZEA-induced BTB destruction, which deepens our understanding of the molecular mechanism of ZEA-induced male reproductive disorders.

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