Abstract

The present study evaluated for the first time changes in the saliva proteome in bitches with pyometra through a high-throughput quantitative proteomic analysis. The aims were to explore whether saliva composition could reflect the physiopathological changes occurring in canine pyometra and to identify potential biomarkers of the disease. Saliva samples from six healthy (H) and six bitches with pyometra (P) were analyzed using tandem mass tags–based approach. Additionally, 15 samples were used for the validation of changes in haptoglobin (Hp) concentration in saliva of dogs with pyometra. Proteomic analysis quantified 707 proteins in saliva. Comparison of the two groups revealed 16 unique proteins significantly modulated in saliva, with S100A calcium-binding protein 12 (S100A12), vimentin, and Hp the most up-regulated in canine pyometra. According to PANTHER (Protein Analysis Through Evolutionary Relationships) classification tool, these proteins are mainly related to proinflammatory mediators, acute-phase proteins, and sepsis. In conclusion, it can be stated that there are changes in various proteins in saliva in canine pyometra reflecting different physiopathological changes occurring in this disease. These proteins could be a source of potential non-invasive biomarkers for this disease that should be confirmed in future studies.

Highlights

  • Pyometra, which literally means “pus-filled uterus,” is the most common disease of the uterus in intact adult bitches after non-pregnant estrus cycles [1]

  • When Hp was measured in saliva, it was significantly higher in bitches with canine pyometra [median (25th−75th percentile) [3.09 (1.39–10.24) μg/mL] in comparison to healthy ones [0.24 (0.19–0.61) μg/mL] (p < 0.001)

  • This is the first study in which salivary proteome was evaluated in bitches with pyometra and compared to healthy controls, showing 16 proteins differentially expressed between the two groups that reflect the activation of different biological pathways and that can potentially be of use as non-invasive biomarkers of this disease

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Summary

Introduction

Pyometra, which literally means “pus-filled uterus,” is the most common disease of the uterus in intact adult bitches after non-pregnant estrus cycles [1]. It is a post-estrum suppurative bacterial infection of the uterus, which may cause accumulation of inflammatory exudate and produces a variety of clinical manifestations [2]. The clinical signs of closed-cervix pyometra are more severe because of the presence of enlarged uterus and endotoxemia, increasing the risks of uterine rupture and the systemic inflammatory response syndrome [3]. There is a scarcity of information regarding the complex pathogenesis of canine pyometra [2], and the knowledge of the changes that occur in saliva proteome in bitches with pyometra could help to clarify this pathogenesis and detect possible potential biomarkers of the disease

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