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

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.

Comparative study of stress response, growth and development of uteri in post‐weaning gilts challenged with zearalenone and estradiol benzoate

“…We observed an increase in the mRNA and protein expression levels of GHR following ZEA and EB treatments compared with the control. This observation raises the question of whether one signalling pathways upregulates the expression of GHR by EB, probably similar to that mediated by ZEA (Zhou, Yang, Shao, et al, 2018a) or other mechanisms. However, the higher decline in GHR expression levels following EB treatment than that with ZEA treatment is contradictory to the uterine index, which creates a new topic of interest for the further research.…”

Assessment of Mycotoxin Exposure in Breastfeeding Mothers with Celiac Disease

“…OTA is carcinogenic in rodents and nephrotoxic in many mammal species; it has been also classified by IARC as possibly carcinogenic to humans and its presence in breast milk has been widely outlined [ 5 ]. The biomonitoring of ZEA is also important due to its toxic effects mainly on the reproductive system [ 6 ]; moreover, ZEA contamination was previously described in breast milk in Italy [ 7 ]. Consumers can be at risk of mycotoxins exposure both directly, by consuming contaminated grains, seeds, and dried fruits, or indirectly, by consuming contaminated animal source food (e.g., milk) derived from animals exposed to these contaminants.…”

The Ethyl Acetate Extract of Gynura formosana Kitam. Leaves Inhibited Cervical Cancer Cell Proliferation via Induction of Autophagy

“…As shown in Figure 5(a) , 60 μ g/ml EAEG treatment for 24 h reduced the cell viability to 64.68%, and this effect was partially offset by the cotreatment with 5 mM 3MA ( Figure 5(a) ), which inhibited significantly the autophagy induced by EAEG ( Figure 5(b) ). Furthermore, EAEG significantly decreased the level of PCNA and MCM7, two widely used cell proliferation markers [ 19 ], and this effect was also partially abrogated by 3MA ( Figure 5(b) ). We thus concluded that EAEG elicited a cytostatic effect on cancer cells through blocking autophagy-mediated cell proliferation rather than inducing apoptosis.…”