Crypt and villus transcriptomic responses in mouse small intestine following oral exposure to hexavalent chromium

Transcriptomic analyses were conducted separately on crypt and villus tissue from formalin-fixed paraffin-embedded transverse duodenal sections from the same study in which microarray-based analyses were previously conducted. A total of 28 groups (7 dose groups x 2 timepoints x 2 tissue compartments) were analyzed for differential gene expression, dose-response, and gene set enrichment. Tissue compartment isolation was confirmed by differences in expression of typical markers of crypt and villus compartments. Fewer than 21 genes were altered in the crypt compartment of mice exposed to 0.1-5 ppm Cr(VI) for 7 or 90 days, which increased to hundreds or thousands of genes at =20 ppm Cr(VI). Consistent with histological evidence for crypt proliferation, a significant, dose-dependent increase in genes that regulate mitotic cell cycle was prominent in the crypt, while subtle in the villus, when compared to samples from time-matched controls. Minimal transcriptomic evidence of DNA damage response in either the crypts or the villi is consistent with published in vivo genotoxicity data. Overall design: Examination of whole transcriptome in the villus and the crypt tissue compartments of FFPE duedenal tissue from mice from six dose groups (plus vehicle controls) orally exposed to Cr(VI) for 7 or 90 days.