Effects Of Zearalenone Exposure Research Articles

Immunotoxicity and uterine transcriptome analysis of the effect of zearalenone (ZEA) in sows during the embryo attachment period

Zearalenone is a mycotoxin and a pollutant that is commonly found in crops. Once ingested, ZEA can cause disturbances in the immune system and produce immunotoxicity. However, there is little research on the effect of ZEA exposure on the relationship between immune regulation and embryo implantation in the uteri of sows. Embryo implantation relies upon the fact that the relationship between the maternal and fetal immune systems is balanced. This balance is provided by the joint regulation of immune organs, cytokines, and uterine immunity. In this study, we investigated 20 sows with an initial weight of 100.00 ± 5.00 kg and 200 days in age. The sows were fed with diets containing ZEA at concentrations of 0 mg/kg, 1 mg/kg, 2 mg/kg, and 10 mg/kg, respectively, from 8 to 14 days of gestation. We studied immunotoxicity and the uterine transcriptomics associated with the effect of ZEA in sows during embryo attachment. Following ZEA treatment, serum biochemical analysis and RT-qPCR were used to detect the concentration and mRNA expression levels of immunoglobulin IgA, IgG, and IgM, in the serum and spleen, respectively. The same analysis was carried out for a range of cytokines in the serum and spleen: IL-1, IL-2, IL-6, IL-10, and TNF. Uterine transcriptome analysis revealed 75, 215, and 81 genes that were differentially expressed in the 0 mg/kg vs 1 mg/kg treatment, 0 mg/kg vs 10 mg/kg treatment, and 1 mg/kg vs 10 mg/kg treatment, respectively. GO terms analysis showed that the up-regulated genes related to the immune system were highly expressed. KEGG pathway analysis further revealed the importance of several metabolic pathways, including drug metabolism-cytochrome P450, the cytokine-cytokine receptor interaction pathway, and calcium signaling pathways. The differentially expressed genes were confirmed by quantitative real-time PCR. These findings expand our understanding of the gene expression profiles and signaling pathways associated with the immune response to ZEA exposure in sows during the embryo implantation window. This study provides valuable information for clarifying the molecular mechanism of ZEA's immunotoxicity to early pregnant sows in the future.

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

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.

Adsorption of modified halloysite nanotubes in vitro and the protective effect in rats exposed to zearalenone

The aim of the present study was to investigate the sorption properties in vitro and the application feasibility of modified halloysite nanotubes (HNT) in reducing the toxic effect of ZEN in rats in vivo. HNT were modified using the surfactant stearyldimethylbenzylammonium chloride. Modified HNT (MHNT) was evaluated using electron microscopy, which revealed that the modification had successfully enlarged the nanotube inner diameter from 11.35 to 20.12 nm. In an in vitro study, the efficiency of MHNT to adsorb zearalenone (ZEN) from simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was investigated in comparison with HNT or a montmorillonite mixture (MON). For all tested adsorbents, the adsorption efficiency for ZEN was increased when the adsorbent dose rose from 0.4 to 1.0 mg/ml and became stable beyond this dose. Moreover, the ZEN adsorption increased with the extension of adsorption times from 20 to 90 min (SGF) and from 30 to 120 min (SIF) without further increase afterwards. Already at the first measuring times (20 and 30 min for SGF and SIF, respectively) MHNT showed a higher adsorptive property then HNT. The ability of MHNT to prevent lesions caused by ZEN was evaluated in 60 female rats. The rats received five experimental diets for two weeks: Control (per kg diet 0.001 mg ZEN); ZEN (0.5 mg ZEN), HNT (0.5 mg ZEN + 1% HNT), MHNT (0.5 mg ZEN + 1% MHNT) and MON (0.5 mg ZEN + 1% MON). The results indicated that the tested adsorbents mitigated toxic and estrogenic effects of ZEN exposure including changes in oxidative stress biomarkers and organ weights. In some parameters (gain, oestradiol content in serum and ZEN concentration in reproductive organs), MHNT exceeded the effectiveness of HNT. Thus, it can be concluded that the modification enhances the adsorbent properties of HNT and that MHNT can bind to ZEN in animal feed or in the gastrointestinal tract.