Dataset Information

Effects of Zearalenone Exposure on the TGF-?1/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-?1 (TGF-?1) 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-?1, 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-?1/Smad3 signaling pathway, suggesting it plays an important role in accelerating the development of the uterus.

SUBMITTER: Zhou M

PROVIDER: S-EPMC5848150 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhou Min M Yang Lijie L Shao Minghui M Wang Yuxi Y Yang Weiren W Huang Libo L Zhou Xuemei X Jiang Shuzhen S Yang Zaibin Z

Toxins 20180123 2

Zearalenone (ZEA) is an estrogenic toxin produced by <i>Fusarium</i> 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 (PCN ...[more]

PMID: 29360780

Similar Datasets

Project description:ObjectiveThis study explored the mechanism of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway under conditions of zearalenone (ZEA)-induced oxidative stress in the duodenum of post-weaning gilts.MethodsForty post-weaning gilts were randomly allocated to four groups and fed diets supplemented with 0, 0.5, 1.0, or 1.5 mg/kg ZEA.ResultsThe results showed significant reductions in the activity of the antioxidant enzymes total superoxide dismutase and glutathione peroxidase and increases the malondialdehyde content with increasing concentrations of dietary ZEA. Immunohistochemical analysis supported these findings by showing a significantly increased expression of Nrf2 and glutathione peroxidase 1 (GPX1) with increasing concentrations of ZEA. The relative mRNA and protein expression of Nrf2, GPX1 increased linearly (p<0.05) and quadratically (p<0.05), which was consistent with the immunohistochemical results. The relative mRNA expression of Keap1 decreased linearly (p<0.05) and quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet. The relative mRNA expression of modifier subunit of glutamate-cysteine ligase (GCLM) increased quadratically (p<0.05) in all ZEA treatment groups and the relative mRNA expression of quinone oxidoreductase 1 (NQO1) catalytic subunit of glutamate-cysteine ligase decreased linearly (p<0.05) and quadratically (p<0.05) in the ZEA1.0 group and ZEA1.5 group. The relative protein expression of Keap1 and GCLM decreased quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet, respectively. The relative protein expression of NQO1 increased linearly (p<0.05) and quadratically (p<0.05) in all ZEA treatment groups in the duodenum.ConclusionThese findings suggest that ZEA regulates the expression of key factors of the Keap1-Nrf2 signaling pathway in the duodenum, which enables resistance to ZEA-induced oxidative stress. Further studies are needed to examine the effects of ZEA induced oxidative stress on other tissues and organs in post-weaning gilts.

Project description:This study aimed to investigate the effect of zearalenone (ZEA) exposure on follicular development in weaned gilts, and its mechanism based on the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) signaling pathway. A total of 32 healthy female weaned piglets (Landrace × Yorkshire × Duroc) with an average body weight of 12.39 ± 0.24 kg were randomly allotted to a basal diet supplemented with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-d feeding test. Blood and ovarian samples were obtained at the end of the experiment to determine serum toxin concentrations, ovarian histology, and the expressions of proliferating cell nuclear antigen (PCNA) and SIRT1/PGC-1α signaling pathway-related genes. Results showed that the vulva area, serum concentrations of ZEA, α-zearalenol and β-zearalenol, the thickness of the growing follicular layer, and the diameter of the largest growing follicles, as well as the expressions of SIRT1, PGC-1α, estrogen-related receptor α (ERRα), ATP synthase subunit beta (ATP5B), and PCNA, increased linearly (P < 0.05) with increasing dietary ZEA, whereas the thickness of the primordial follicle layer decreased linearly (P < 0.05). Immunohistochemical analysis showed that the immunoreactive substances of SIRT1 and PGC-1α in the ovaries enhanced with the increasing dietary ZEA (P < 0.05). In addition, the thickness of the growing follicular layer and the diameter of the largest growing follicle were positively correlated with relative mRNA and protein expressions of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). However, the thickness of the primordial follicle layer was negatively correlated with the mRNA and protein expression of SIRT1, PGC-1α, ERRα, ATP5B, and PCNA (P < 0.05). Interestingly, the 1.5 mg/kg ZEA treatment had highly hyperplastic follicles, whereas 3.0 mg/kg ZEA resulted in a large number of follicular atresia, which indicated that low-dose ZEA exposure accelerated follicular proliferation, while high-dose ZEA promoted follicular atresia, although the critical value interval needs further confirmation. Results provide a theoretical basis for finding the therapeutic target of ZEA-induced reproductive disorders in weaned gilts.

Dataset Information

Effects of Zearalenone Exposure on the TGF-?1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets