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Zearalenone promotes apoptosis of mouse Leydig cells by targeting phosphatase and tensin homolog and thus inhibiting the PI3K/AKT signal pathway

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Abstract

Zearalenone (ZEA) is a mycotoxin with estrogenic activity whose main effect is to impair the reproductive systems of animals. It leads to reproductive disorders in livestock and thus causes serious losses to agriculture and animal husbandry. This study aims to examine whether ZEA induces toxicity in Leydig cells through the PI3K/AKT signaling pathway and also to investigate the role played by the upstream phosphatase and tensin homolog (PTEN) gene. An adenovirus vector model was constructed to interfere with the PTEN gene to investigate whether ZEA promotes the apoptosis of TM3 cells through the PI3K/AKT pathway. Apoptosis was detected cytometrically and the protein expression levels of PTEN, AKT, p-AKT, Bax, and Bcl-2 were evaluated via western blot analysis. The results show that ZEA induces apoptosis of TM3 cells. PTEN expression is significantly increased (P < 0.01), Bax expression is increased (P < 0.05), AKT and p-AKT expression of anti-apoptotic protein is significantly decreased (P < 0.01), and Bcl-2 protein expression is decreased (P < 0.05) in the ZEA group compared with the control group. In the shRNA+ZEA group, the expression levels of PTEN and Bax proteins are significantly decreased (P < 0.01), AKT protein is significantly increased (P < 0.01), and p-AKT protein is increased (P < 0.05) compared with the ZEA group. This study thus demonstrates that ZEA promotes apoptosis of TM3 cells by targeting PTEN and thus inhibiting the PI3K/AKT signal pathway.

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Funding

This work was financially supported by the National Natural Science Foundation of China (31872538, 31772809, 31972746).

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  1. Jia Chen and Mingyang Wang contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, 110866, China

    Jia Chen, Mingyang Wang, Hanli Wang & Miao Long

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  1. Jia Chen
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Contributions

J.C. wrote the paper; .M.W. and H.W. investigated; M.L. revised and supervised. All authors read and approved the final manuscript.

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Correspondence to Miao Long.

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Responsible Editor: Mohamed M. Abdel-Daim

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Chen, ., Wang, M., Wang, H. et al. Zearalenone promotes apoptosis of mouse Leydig cells by targeting phosphatase and tensin homolog and thus inhibiting the PI3K/AKT signal pathway. Environ Sci Pollut Res 28, 67779–67787 (2021). https://doi.org/10.1007/s11356-021-15282-7

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  • DOI: https://doi.org/10.1007/s11356-021-15282-7

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