Cystic
endometrial hyperplasia (CEH), mucometra, and
pyometra are common
uterine diseases in intact dogs, with
pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential
biomarkers for closed-cervix
pyometra, the most severe condition. Total
RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17
pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all
pyometra samples. When comparing
pyometra with other groups, 189 differentially expressed genes were detected. SLPI,
PTGS2/COX2, MMP1, S100A8, S100A9 and
IL8 were among the top up-regulated genes detected in
pyometra, further confirmed by external expression data. Notably, a particular molecular profile in
pyometra from animals previously treated with exogenous
progesterone compounds was observed in comparison with
pyometra from untreated dogs as well as with other groups irrespective of exogenous
hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory
cytokines IL1B, TNF and
IL6 as well as LTF were detected in the
pyometra from treated animals. Interestingly, closed
pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential
biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that
pyometra from
progesterone treated dogs is a distinct molecular entity.