Thiram-induced changes in the expression of genes relating to vascularization and tibial dyschondroplasia.
Tibial dyschondroplasia (TD), a major metabolic cartilage disease in poultry, is characterized by the distension of proximal growth plates of tibia that 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 posthatch and the expression of the genes for vascular endothelial growth factor (VEGF), its receptors (VEGFR1 and VEGFR2), and an antiapoptotic protein (Bcl-2) were determined in the growth plate cartilage at 48 and 166 h after feeding thiram. Reverse transcription 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 the 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 downregulated 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.
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Poultry Production and Product Safety Research Unit, Agricultural Research Service, USDA, Fayetteville, AR 72701, USA. nrath@uark.edu
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D000818:Animals; D002645:Chickens / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006132:Growth Plate / Q000187:drug effects / Q000254:growth & development; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000139:chemically induced* / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013893:Thiram / Q000494:pharmacology*; D013977:Tibia / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D013893:Thiram; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2