Title: Thiram-Induced Changes in the Expression of Genes Relating to Vascularization and Tibial Dyschondroplasia. Authors
Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 16, 2007
Publication Date: November 1, 2007
Citation: Rath, N.C., Huff, W.E., Huff, G.R. 2007. Thiram-induced changes in the expression of genes relating to vascularization and tibial dyschondroplasia. Poultry Science. 86(11):2390-2395. Interpretive Summary: Thiram, a common pesticide induces lameness in poultry because it prevents proper development leg bones. To understand how this chemical produces this changes we focused on the mechanisms that produce blood vessel growth because blood vessel growth is important in bone development. We found that this pesticide not only impairs some of the mechanisms of bone formation but also causes the death of cells that are normally needed for bone formation.
Technical Abstract: Tibial dyschondroplasia (TD), a major metabolic cartilage disease in poultry, is characterized by the distension of proximal growth plates of tibia which fail to form bone, lack blood vessels, and contain nonviable cells. Thiram, a carbamate pesticide, when fed to young broiler chicks induces TD with high regularity and precision. We used this experimental model to understand the cause of the defects associated with TD by determining the expression of selective candidate genes associated with vascularization and cell survival. Week-old broiler chickens were fed 100 ppm thiram for 48 h between d 8 and 10 post hatch and the expression of the genes for vascular endothelial growth factor (VEGF), its receptors, VEGFR1 and VEGFR2, and an anti-apoptotic protein Bcl-2, were determined in the growth plate cartilage at 48 and 166 h after feeding thiram. RT-PCR and capillary electrophoresis were used to determine the expression of these genes relative to the 18S gene as an internal standard. There was an increase in the expression of VEGF gene by thiram at 48 h which remained elevated above the control level at 166 h. A suppression of genes encoding both VEGF receptors and Bcl-2 was evident at 48 h in thiram-fed chickens when there was no visible distension of growth plate indicative of TD. At 166 h however, there was a significant distension of growth plates in thiram treated birds with a high percentage of cells derived from these tissues exhibiting characteristics of dead cells. Although the expressions of VEGF receptors were low at 166 h in thiram treated birds, they were not statistically different from controls; the Bcl-2 gene expression however, remained significantly down regulated in those birds. It appears that some of the early effects of thiram on the growth plate may be the failure of genes encoding VEGF receptors and Bcl-2 resulting from endothelial cell death which compromise vascularization, cartilage remodeling, and the removal of dead chondrocytes leading to TD lesions.