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

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.

Köpeklerde Endotoksik Pyometranın Klinik, Bakteriyolojik ve Histopatolojik Özellikleri

“…could also been detected [11,22,23] . It has been established that if E. coli migrates to the uterus, it binds with higher affinity to the endometrium and myometrium layers and constitutes a resistance to the uterus' defense mechanisms such as lactoferrin and mucin-1 [24][25][26][27] . As reported in previous studies [4,11,23,28] , gram negative bacteria (75%) such as E. coli, Klebsiella spp.…”

Canine pyometra: What is new?

“…In recent years, new omics technologies and rapid sequencing methods have been developed, which has prompted possibilities for new studies. One study of gene activation identified 29 genes that are upregulated during the disease (Voorwald et al., ). Importantly, products of the upregulated genes are possible diagnostic indicators for use in clinical practice if rapid and cost‐effective diagnostic tests are developed (Bukowska et al., ; Chu Py, Salamonsen, Lee, & Wright, ; Hagman, Rönnberg, & Pejler, ; Silva et al., ).…”

Study of innate factors in the local immune defense of the genital organs of dogs and cats

“…Immune system of reproductive organs of animals is represented by a number of cellular and humoral protective factors. Recently, scientists from different countries of the world are increasingly attracted by the role of immune cells in the formation of immune homeostasis in the body of animals (Hagman et al, 2009;Sheldon et al, 2010;Voorward et al, 2015). After all, Immune responses are important at all stages of the formation of the reproductive system of animals and have a regulating effect in different periods of their reproductive ability (Silva et al, 2012;Amos et al, 2014;Wira et al, 2015).…”