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Toxins 2018, 10(2), 49; https://doi.org/10.3390/toxins10020049

Effects of Zearalenone Exposure on the TGF-β1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts

1
Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Department of Animal Sciences and Technology, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China
2
Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, AB T1J 4B1, Canada
*
Authors to whom correspondence should be addressed.
Received: 11 December 2017 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 23 January 2018
(This article belongs to the Special Issue Impact of Human Metabolism on the Toxicological Effects of Mycotoxins)
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Abstract

Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is widely distributed and posed a great health risk to both humans and farm animals. Reproductive disorders associated with ZEA such as premature puberty, infertility and abortion have plagued the animal husbandry, but the molecular mechanism is unclear. Because transforming growth factor-β1 (TGF-β1) signaling pathway is involved in the proliferation and apoptosis of cells, proliferating cell nuclear antigen (PCNA), B-cell lymphoma/leukemia-2 (BCL-2) and BCL-2 associated X protein (BAX) that all play indispensable roles in the normal development of the uterus, it is hypothesized that ZEA induces reproductive disorders is closely related to the expression of these genes. The objective of this study was to assess the effects of dietary ZEA at the concentrations of 0.5 to 1.5 mg/kg on the mRNA and protein expression of these genes in the uteri of post-weaning gilts and to explore the possible molecular mechanism. Forty healthy post-weaning female piglets (Duroc × Landrace × Large White) aged 38 d were randomly allocated to basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d. Piglets were euthanized at the end of the experiment and samples were taken and subjected to immunohistochemistry, qRT-PCR and Western blot analyses. The relative mRNA expressions of PCNA, BCL-2 and Smad3 in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.05) as ZEA concentration increased in the diet. The relative protein expressions of PCNA, BAX, BCL-2, TGF-β1, Smad3, and phosphorylated Smad3 (p-Smad3) in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.001) with an increasing level of ZEA. The results showed that uterine cells in the ZEA (0.5–1.5 mg/kg) treatments were in a high proliferation state, indicating that ZEA could accelerate the proliferation of uteri and promote the development of the uteri. At the same time, the results suggested that ZEA activates the TGF-β1/Smad3 signaling pathway, suggesting it plays an important role in accelerating the development of the uterus. View Full-Text
Keywords: zearalenone; proliferating cell nuclear antigen; B-cell lymphoma/leukemia-2; BCL-2 associated X protein; TGF-β1/Smad3 pathway zearalenone; proliferating cell nuclear antigen; B-cell lymphoma/leukemia-2; BCL-2 associated X protein; TGF-β1/Smad3 pathway
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Zhou, M.; Yang, L.; Shao, M.; Wang, Y.; Yang, W.; Huang, L.; Zhou, X.; Jiang, S.; Yang, Z. Effects of Zearalenone Exposure on the TGF-β1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts. Toxins 2018, 10, 49.

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