Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice

Abstract

Ureaplasma diversum is an opportunistic pathogen associated with uterine infl ammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profi le of circulating blood cells. Morphological changes, intensity of infl ammation and the production of cytokines were compared. The infected mice showed local infl ammation through the production of IFN-γ and TNF-α. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-infl ammatory cytokines in uterine parenchyma. The levels of TNF-α of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the fi rst report of an intrauterine infection model in mice.

Ureaplasma diversum and Its Membrane-Associated Lipoproteins Activate Inflammatory Genes Through the NF-κB Pathway via Toll-Like Receptor 4

“…In the present study, the expression of Pro-inflammatory genes following Ureaplasma infection was dose dependent. Silva et al (2016) detected a higher TNF-α production in intrauterine infection with 10 6 and 10 8 U. diversum /mL and a lower response happened with 10 4 organisms/mL ( Silva et al, 2016 ). Likewise, U. diversum was also able to induce TNF-α production in mouse macrophages in a dose dependent model ( Chelmonska-Soyta et al, 1994 ).…”

“…At the logarithmic growth (colorimetric broth changes), the culture was centrifuged at 21,400 × g for 25 min at 20°C. The pellet was homogenized in phosphate buffered saline (PBS) ( Silva et al, 2016 ) and the culture suspension was quantified in 96 well microplates to obtain an inoculum based on Colorimetric Change Units ( Ureaplasma /mL) ( Kim et al, 1994 ). 10 6 , 10 5 , and 10 4 Ureaplasma /mL for U. diversum ATCC 49782 and 10 5 , 10 4 , and 10 3 Ureaplasma /mL for U. diversum CI-GOTA were used in this study.…”

Ureaplasma diversum Genome Provides New Insights about the Interaction of the Surface Molecules of This Bacterium with the Host

“…U . diversum also was capable of inducing significant TNF-alpha production in the uterus of experimentally infected mice [ 16 ], which indicates that the presence of this microorganism in the reproductive tract of females may significantly alter the homeostasis of the uterus microenvironment. Nevertheless, the molecular mechanisms by which this organism exerts its virulence and pathogenicity on such cells and tissues are mostly unknown [ 1 , 15 , 17 , 18 ].…”

Assessment of cow and farm level risk factors associated with Ureaplasma diversum in pasture-based dairy systems - A field study

“…diversum can be detected inside cells or adhered to their surfaces (Marques et al 2010) and induced significant TNF-alpha production in the uterus of mice (Silva et al 2016), indicating that the colonization of the reproductive tract of females may alter the homeostasis of the uterus microenvironment . Recent studies using the metagenomic to evaluate the progression of the uterine microbiota from calving until establishment of metritis have shown that among 824 bacteria genera found in uterine samples of metritic and non metritic cows, Ureaplasma was present in 5.2%, with a relative increasing in the number of positive samples for this bacterium from 0 to 2 days post partum, and then decreasing from 2 to 6 ± 2 days post partum (Jeon et al 2015).…”