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Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

Voorwald FA, Marchi FA, Villacis RA, Alves CE, Toniollo GH, Amorim RL, Drigo SA, Rogatto SR - PLoS ONE (2015)

Bottom Line: Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array.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.This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Veterinary Clinic and Department of Surgery, São Paulo State University (UNESP), Jaboticabal, São Paulo, Brazil.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Hierarchical clustering analysis.Dendogram resulted from unsupervised analysis including diestrus, cystic endometrial hyperplasia (CEH), mucometra and pyometra samples. Cervix condition, estrus cycle phase and previous exogenous progesterone treatment status for each sample are shown.
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pone.0133894.g001: Hierarchical clustering analysis.Dendogram resulted from unsupervised analysis including diestrus, cystic endometrial hyperplasia (CEH), mucometra and pyometra samples. Cervix condition, estrus cycle phase and previous exogenous progesterone treatment status for each sample are shown.

Mentions: Unsupervised hierarchical clustering analysis revealed two main clusters, with mucometra and pyometra samples showing a strong trend to cluster together, and diestrus and CEH samples mainly grouped in the other cluster (Fig 1). Pyometra showed 189 differentially expressed genes in comparison with other groups (diestrus, CEH and mucometra), with 169 overexpressed and 20 underexpressed (S2 Table). The SLPI (secretory leukocyte peptidase inhibitor) gene was detected as having the highest fold change, being 30 times more expressed in pyometra compared with other endometrial tissues (S2 Table). Among the highest upregulated genes in pyometra, three metalloproteinase genes (MMP13, MMP1 and MMP12) and three S100 family members (S100A12, S100A8 and S100A9) were observed. Conversely, the EPHA7 (ephrin receptor A7) gene was detected as having the lowest fold change in pyometra.


Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

Voorwald FA, Marchi FA, Villacis RA, Alves CE, Toniollo GH, Amorim RL, Drigo SA, Rogatto SR - PLoS ONE (2015)

Hierarchical clustering analysis.Dendogram resulted from unsupervised analysis including diestrus, cystic endometrial hyperplasia (CEH), mucometra and pyometra samples. Cervix condition, estrus cycle phase and previous exogenous progesterone treatment status for each sample are shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519320&req=5

pone.0133894.g001: Hierarchical clustering analysis.Dendogram resulted from unsupervised analysis including diestrus, cystic endometrial hyperplasia (CEH), mucometra and pyometra samples. Cervix condition, estrus cycle phase and previous exogenous progesterone treatment status for each sample are shown.
Mentions: Unsupervised hierarchical clustering analysis revealed two main clusters, with mucometra and pyometra samples showing a strong trend to cluster together, and diestrus and CEH samples mainly grouped in the other cluster (Fig 1). Pyometra showed 189 differentially expressed genes in comparison with other groups (diestrus, CEH and mucometra), with 169 overexpressed and 20 underexpressed (S2 Table). The SLPI (secretory leukocyte peptidase inhibitor) gene was detected as having the highest fold change, being 30 times more expressed in pyometra compared with other endometrial tissues (S2 Table). Among the highest upregulated genes in pyometra, three metalloproteinase genes (MMP13, MMP1 and MMP12) and three S100 family members (S100A12, S100A8 and S100A9) were observed. Conversely, the EPHA7 (ephrin receptor A7) gene was detected as having the lowest fold change in pyometra.

Bottom Line: Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array.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.This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies.

View Article: PubMed Central - PubMed

Affiliation: Veterinary Clinic and Department of Surgery, São Paulo State University (UNESP), Jaboticabal, São Paulo, Brazil.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus