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

Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, 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 profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation 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-inflammatory 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 first report of an intrauterine infection model in mice.

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Endometrial Microbiome and Women’s Reproductive Health – Review of the Problem Endometrial Microbiome and Reproductive Health

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.4.03 ◽

2021 ◽

Author(s):

Tatyana Bodurska ◽

Emiliana Konova ◽

Svetlana Pachkova ◽

Angel Yordanov

Keyword(s):

Reproductive Health ◽

Reproductive Tract ◽

Embryo Implantation ◽

Normal Pregnancy ◽

Uterine Contractions ◽

The Past ◽

Uterine Inflammation ◽

Immunological Homeostasis ◽

Inflammatory Molecules ◽

Health Review

Currently, unlike in the past, the endometrial cavity is not considered to be sterile. The endometrium is supposed to be dominated by Lactobacilli, but also their deficiency can be found in the reproductive tract of asymptomatic healthy women. Sometimes the endometrial microbiome is dominated by various pathological microorganisms, and this can lead to various conditions as chronic endometritis, chorioamnionitis and preterm birth. Their presence causes uterine inflammation and infection, release of pro-inflammatory molecules, uterine contractions, disruption of cervical barrier, premature rupture of membranes. Uterine dysbiosis is associated with recurrent implantation failure and recurrent miscarriages. As the microbiome is important for maintaining immunological homeostasis at the level of gastrointestinal tract Lactobacilli may play a similar function at the level of uterus. The lactobacillus-dominated uterine microbiome is of great importance for maintaining a hostile uterine microenvironment, embryo implantation, early pregnancy development and normal pregnancy outcome.

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Postpartum ovulation and early pregnancy in the menstruating spiny mouse, Acomys cahirinus

Scientific Reports ◽

10.1038/s41598-021-84361-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jarrod McKenna ◽

Nadia Bellofiore ◽

Evdokia Dimitriadis ◽

Peter Temple-Smith

Keyword(s):

Early Pregnancy ◽

Reproductive Tract ◽

Morphological Changes ◽

Embryo Implantation ◽

Morphological Evidence ◽

Enzyme Linked Immunosorbent Assay ◽

Spiral Artery ◽

Stromal Invasion ◽

Spiny Mice ◽

Histology And Immunohistochemistry

AbstractEgyptian spiny mice are the only known species to have human-like menstruation and a postpartum ovulation. Unfortunately, no endocrine or morphological evidence has been provided for a postpartum ovulation in spiny mice, and while later stages of pregnancy have been well studied, early events including embryo implantation and spiral artery remodelling have not been reported. This study compared the sex steroid endocrinology and reproductive tract morphology of dams at eight timepoints (n = 40) postpartum to determine the timing of ovulation and the timing and invasiveness of embryo implantation in A. cahirinus. Reproductive tracts were fixed and stained for histology and immunohistochemistry, and plasma was prepared for enzyme-linked immunosorbent assay. Ovarian histology and estradiol-17B concentrations indicate ovulation within 48 h of parturition and then immediate resumption of follicular growth. Uterine histology and immunohistochemistry revealed progressive epithelial repair, endometrial growth and spiral artery assembly and remodelling in dams postpartum. Blastocysts were seen in the uterine lumen at day 4–5 postpartum and embryos had implanted superficially with minimal stromal invasion by day 5–6. This study provides further evidence for the unique, humanesque reproductive biology of spiny mice and for a postpartum ovulation using endocrine and morphological changes observed during early pregnancy. Taken together, our data suggest that spiny mice may act as appropriate models of human pregnancy disorders such as implantation failure or pre-eclampsia.

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Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽

10.3390/molecules25163573 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3573

Author(s):

Lian-Chun Li ◽

Zheng-Hong Pan ◽

De-Sheng Ning ◽

Yu-Xia Fu

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Morphological Changes ◽

Raw264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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Development of an intrauterine infection model in the postpartum dairy cow

New Zealand Veterinary Journal ◽

10.1080/00480169.2021.1950069 ◽

2021 ◽

pp. 1-18

Author(s):

S McDougall ◽

EM Graham ◽

D Aberdein ◽

CB Reed ◽

CR Burke

Keyword(s):

Dairy Cow ◽

Intrauterine Infection ◽

Infection Model

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Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽

10.1210/en.2018-00105 ◽

2018 ◽

Vol 159 (6) ◽

pp. 2459-2472 ◽

Cited By ~ 2

Author(s):

Yan Yin ◽

Adam Wang ◽

Li Feng ◽

Yu Wang ◽

Hong Zhang ◽

...

Keyword(s):

Signal Transduction ◽

Heparan Sulfate ◽

Signaling Pathways ◽

Reproductive Tract ◽

Ovarian Function ◽

Embryo Implantation ◽

Uterine Epithelium ◽

Female Reproductive Tract ◽

Uterine Receptivity ◽

Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

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Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

Microbiology ◽

10.1099/mic.0.028464-0 ◽

2009 ◽

Vol 155 (8) ◽

pp. 2612-2619 ◽

Cited By ~ 21

Author(s):

Lisa K. Nelson ◽

Genevieve H. D'Amours ◽

Kimberley M. Sproule-Willoughby ◽

Douglas W. Morck ◽

Howard Ceri

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Tissue Damage ◽

Inflammatory Markers ◽

Bacterial Colonization ◽

Opportunistic Pathogen ◽

Infection Model ◽

Chronic Infections ◽

Strain Pao1 ◽

Rat Prostate

Pseudomonas aeruginosa frequently acts as an opportunistic pathogen of mucosal surfaces; yet, despite causing aggressive prostatitis in some men, its role as a pathogen in the prostate has not been investigated. Consequently, we developed a Ps. aeruginosa infection model in the rat prostate by instilling wild-type (WT) Ps. aeruginosa strain PAO1 into the rat prostate. It was found that Ps. aeruginosa produced acute and chronic infections in this mucosal tissue as determined by bacterial colonization, gross morphology, tissue damage and inflammatory markers. WT strain PAO1 and its isogenic mutant PAO-JP2, in which both the lasI and rhlI quorum-sensing signal systems have been silenced, were compared during both acute and chronic prostate infections. In acute infections, bacterial numbers and inflammatory markers were comparable between WT PA01 and PAO-JP2; however, considerably less tissue damage occurred in infections with PAO-JP2. Chronic infections with PAO-JP2 resulted in reduced bacterial colonization, tissue damage and inflammation as compared to WT PAO1 infections. Therefore, the quorum-sensing lasI and rhlI genes in Ps. aeruginosa affect acute prostate infections, but play a considerably more important role in maintaining chronic infections. We have thus developed a highly reproducible model for the study of Ps. aeruginosa virulence in the prostate.

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Long Noncoding RNA SNHG1 Promotes Lipopolysaccharide-Induced Activation and Inflammation in Microglia via Targeting miR-181b

NeuroImmunoModulation ◽

10.1159/000514549 ◽

2021 ◽

pp. 1-11

Author(s):

Jun Dong ◽

Tingkai Fu ◽

Yunxue Yang ◽

Zhenxin Mu ◽

Xingang Li

Keyword(s):

Inflammatory Cytokines ◽

Long Noncoding Rna ◽

Calcium Binding ◽

Noncoding Rna ◽

Morphological Changes ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Inflammation Response ◽

Tnf Α ◽

Cox 2

Introduction: Long noncoding RNA small nuclear host gene 1 (SNHG1) was involved in neuroinflammation in microglial BV-2 cells; however, its interaction with microRNA (miR)-181b in lipopolysaccharide (LPS)-induced BV-2 cells remained poor. Methods: BV-2 cells were treated with LPS and then were subjected to observation on morphology and immunofluorescence staining. After transfection, levels of inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were determined with enzyme-linked immunosorbent assay (ELISA). The potential binding sites between SNHG1 and miR-181b were confirmed using dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction and Western blot were applied for detecting the mRNA and protein expressions of proinflammatory cytokines, ionized calcium-binding adapter molecule 1 (Iba1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Results: LPS led to the morphological changes and activation of BV-2 cells. The transfection of SNHG1 overexpression vector further promoted LPS-induced SNHG1 upregulation, inflammatory cytokines (IL-1β, IL-6, and TNF-α) generation and Iba-1, COX-2, and iNOS expressions, whereas silencing SNHG1 did the opposite. miR-181b functions as a downstream miRNA of SNHG1. In LPS-treated cells, the inhibition of miR-181b induced by SNHG1 promoted inflammation response and the expressions of Iba-1, COX-2, and iNOS. Conclusion: SNHG1 was involved in LPS-induced microglial activation and inflammation response via targeting miR-181b, providing another evidence of the roles of SNHG1 implicated in neuroinflammation of microglia.

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Diet-induced obesity promotes systemic inflammation and increased susceptibility to murine visceral leishmaniasis

Parasitology ◽

10.1017/s003118201600127x ◽

2016 ◽

Vol 143 (12) ◽

pp. 1647-1655 ◽

Cited By ~ 5

Author(s):

GLÊNIA DAROS SARNÁGLIA ◽

LUCIANA POLACO COVRE ◽

FAUSTO EDMUNDO LIMA PEREIRA ◽

HERBERT LEONEL DE MATOS GUEDES ◽

ANA MARIA CAETANO FARIA ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Systemic Inflammation ◽

Morphological Changes ◽

Control Diet ◽

Parasite Burden ◽

Diet Group ◽

Cell Hyperplasia ◽

Diet Induced Obesity ◽

Tnf Α ◽

Increased Susceptibility

SUMMARYObesity is the main causal factor for metabolic syndrome and chronic systemic inflammation, which impacts on immune function and increases susceptibility to pathogens. Here, we investigated the effect of obesity on the outcome of visceral leishmaniasis caused by Leishmaniasis infantum chagasi. C57BL/6 mice fed with high-sugar and butter diet (HSB) showed a significant increase in body weight, adiposity index and morphological changes in adipocyte. To investigate the consequences of obesity on the specific immunity against Leishmania, both control and HSB diet groups were infected with 107L. infantum chagasi promastigotes in the eighth-week after diet started and euthanized 4 weeks later. HSB-diet fed mice exhibited a significantly higher parasite burden in both liver and spleen compared with control- diet group. Gonadal adipocyte tissue from HSB-diet mice showed increased TNF-α, IL-6 and leptin and diminished IL-10 production compared with control. Cytokines production analysis in the spleen and liver from these animals also demonstrated higher production of IFN-γ, TNF-α, IL-6 and nitric oxide and diminished production of IL-10 and TGF-β, which correlate with inflammatory foci and the cell hyperplasia observed. Taken together, obesity can interfere with responses to pathogen-derived signals and impair the development of protective anti-Leishmania immunity.

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Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Expo-Sure in Rats

Antioxidants ◽

10.3390/antiox10121906 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1906

Author(s):

Mayada R. Farag ◽

Attia A. A. Moselhy ◽

Amany El-Mleeh ◽

Samira H. Aljuaydi ◽

Tamer Ahmed Ismail ◽

...

Keyword(s):

Antioxidant Status ◽

Fruits And Vegetables ◽

Caspase 3 ◽

Chemotherapeutic Agent ◽

Morphological Changes ◽

Apoptotic Markers ◽

Tnf Α ◽

Chemotherapy Patients ◽

The Impact ◽

Cat Gene

Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) and in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.

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Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – II Infection with Persister Forms of Staphylococcus aureus Causes a Chronic Persistent Skin Infection with More Severe Lesion that Takes Longer to Heal and is not Eradicated by the Current Recommended Treatment in Mice

10.1101/476465 ◽

2018 ◽

Cited By ~ 2

Author(s):

Rebecca Yee ◽

Yuting Yuan ◽

Cory Brayton ◽

Andreina Tarff Leal ◽

Jie Feng ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Stationary Phase ◽

Skin Infection ◽

Bacterial Load ◽

Mouse Skin ◽

Infection Model ◽

Persister Cells ◽

Persistent Infections ◽

Recommended Treatment ◽

Biofilm Bacteria

AbstractStaphylococcus aureus is an opportunistic pathogen that can cause persistent infections clinically. Treatment for chronic S. aureus infections ranges from at least one week to several months and such infections are prone to relapse likely due to the presence of persistent forms of bacteria such as persister cells. Persister cells, which are bacterial cells that become dormant under stress conditions, can be isolated in vitro but their clinical significance in in vivo infections are largely unclear. Here, we evaluated S. aureus persistent forms using stationary phase cultures and biofilm bacteria (enriched in persisters) in comparison with log phase cultures in terms of their ability to cause disease in a mouse skin infection model. Surprisingly, we found that infection of mice with stationary phase cultures and biofilm bacteria produced a more severe chronic skin infection with more pronounced lesions which took longer to heal than log phase (actively growing) cultures. After two week infection, the bacterial load and skin tissue pathology, as determined by hyperplasia, immune cell infiltration, and crust/lesion formation, of mice infected with the more persistent forms (e.g. stationary phase bacteria and biofilm bacteria) were greater than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in the treatment study, despite reducing lesion sizes and pathology in infected mice. Analogous findings were also observed in a Caenorhabditis elegans model, where S.aureus stationary phase cultures caused a greater mortality than log phase culture as early as two days post-infection. Thus, we established a new model for chronic persistent infections using persister bacteria that could serve as a relevant model to evaluate therapeutic options for persistent infections in general. Our findings connect persisters with persistent infections, have implications for understanding disease pathogenesis, and are likely to be broadly valid for other pathogens.

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