Gene expression profile associated with thymus regeneration in dexamethasone-treated beef cattle

Abstract

Glucocorticoids (GCs) are illegally used as growth promoters in cattle, and the analytical methods officially applied most likely underestimate the precise frequency of the abuse. As a side effect, the administration of GCs causes fat infiltration, apoptosis, and atrophy of the thymus. However, gross and histological observations carried out previously showed that the thymus preserves an intrinsic ability to regenerate. The aim of this work was to study the transcriptional effects of GCs on genes likely involved in regeneration of the epithelial cell network in the cervical and thoracic thymus of beef cattle treated with dexamethasone (DEX) or prednisolone (PRD) in comparison with a control group. Moreover, the ratio of bax/bcl2 genes was examined to verify a possible antiapoptotic activity occurring at the same time. In the cervical thymus, DEX administration increased the gene expression of c-myc (P < 0.01), tcf3 (P < 0.05), tp63 (P < 0.01), and keratin 5 (krt5; P < 0.01). In the thoracic thymus of DEX-treated cattle, the gene expression of tcf3 (P < 0.01), tp63 (P < 0.01), and krt5 (P < 0.05) was increased. These results suggested that thymic regeneration is underway in the DEX-treated animals. However, the bax/bcl2 ratio was decreased in both cervical and thoracic thymus of DEX-treated cattle (P < 0.01 and P < 0.05, respectively), showing an antiapoptotic effect through the mitochondrial pathway. Conversely, PRD administration caused no change in the expression of all considered genes. These results sustain the hypothesis that regeneration occurs in the thymus parenchyma 6 d after the DEX treatment was discontinued. This hypothesis is also supported by the absence of alterations in the thymus of PRD-treated beef cattle. Indeed, previous studies showed the inability of PRD to induce macroscopic and microscopic lesions in the thymus. Therefore, in this context, it is not surprising that PRD induced no alteration of genes involved in the regeneration pathway.