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Analysis of transcriptional differences between ZIKV-infected Ifnar-/- and Ifnar+/- placentas

ABSTRACT: Purpose: While type I interferons (IFN) are important for control of viral replication, we see that, upon infection of Ifnar-/- females were crossed to Ifnar+/- males with ZIKV, only Ifnar+/- fetuses are resorbed or develop severe growth restriction. To identify how IFN may be altering placenta development, we performed RNAsequencing on infected and uninfected Ifnar-/- and Ifnar+/- placentas. Methods: Ifnar-/- females were crossed to Ifnar+/- males and infected intravaginally with Cambodian ZIKV at E5.5. Placentas were harvested from infected and uninfected pregnant dams at E10.5. Results/ Conclusions: Comparison of ZIKV-infected Ifnar-/- and Ifnar+/- shows an elevated interferon stimulated gene (ISG) signature in Ifnar+/- placentas but does not reveal any underlying developmental defects that may be causing defects in placenta development.

ORGANISM(S): Mus musculus

PROVIDER: GSE98423 | GEO | 2017/12/31

SECONDARY ACCESSION(S): PRJNA385077

REPOSITORIES: GEO

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Mus musculus

Project description:Analysis of transcriptional differences between ZIKV-infected Ifnar-/- and Ifnar+/- placentas

| PRJNA385077 | ENA

Decreased CSTB, RAGE and Axl receptor is associated with Zika infection in the human placenta

Project description:Zika virus (ZIKV) compromises the placental integrity infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection, are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in inflammation. The purpose of this work iis work aims to investigate CSTB, RAGE, and AXL receptor expression in ZIKV infected placental tissues at term. The hypothesis is that in ZIKV-infected placenta, there is overexpression of CSTB and increased inflammation affecting the RAGE and AXL receptor expression. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and Western Blot analysis were performed to analyze proteins and pathways affected by ZIKV infection in frozen placenta. Pathological The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblasts layer, and cell agglutination associated to with ZIKV infection of placental tissue. ZIKV infection was mostly localized to the trophoblast layer. There was a significant decrease in the expression of CSTB, RAGE and AXLCSTB, RAGE and AXL expression in ZIKV positive placenta. This downregulation can impair immune responses and facilitate virus penetration into the placenta. Results are consistent with our previous studies and literature of on ZIKV infection by activation ofng Inflammasome and Pyroptosis through caspase 1 upregulation and affecting the cellular structure, tissue remodeling, and cell differentiation by upregulation of tubulin beta and heat shock protein 27.

2023-03-11 | PXD037388 | Pride

Untargeted_Urine_Carnitine_Efficacy_Study_Males_Females

Project description:5-week old male and female Swiss Webster mice were infected with 500,000 Trypanosoma cruzi strain Sylvio X10/4 parasites. Urine was collected from uninfected mice pre-infection, from infected and uninfected mice every week for 5 weeks post infection, from infected and uninfected mice 67 (females)/68 (males) days post infection, and from infected and uninfected mice 117 (females)/124 (males) days post infection for acute, mid-chronic, and chronic time-points. Metabolites were extracted with methanol and an untargeted LCMS analysis was ran on a Thermo Q Exactive Plus instrument with a Phenomenex Luna Omega Polar C18 column.

2022-03-23 | MSV000089112 | MassIVE

Targeted_PRM_Urine_Carnitine_Efficacy_Study_Males_Females

Project description:5-week old male and female Swiss Webster mice were infected with 500,000 Trypanosoma cruzi strain Sylvio X/104 parasites. Urine was collected from uninfected mice pre-infection, from infected and uninfected mice every week for 5 weeks post infection, from infected and uninfected mice 67 (females)/68 (males) days post infection, and from infected and uninfected mice 117 (females)/124 (males) days post infection for acute, mid-chronic, and chronic time-points. Metabolites were extracted with methanol and a targeted PRM LCMS analysis was ran on a Thermo Q Exactive Plus instrument with a Phenomenex Luna Omega Polar C18 column.

2022-03-23 | MSV000089113 | MassIVE

Transcriptional analysis of ZIKV-infected Ifnar-/- and Ifnar+/- placentas and IFN-beta (IFN-b) or IFN-lambda (IFN-l) treated human mid-gestation chorionic villus explants

Project description:Transcriptional analysis of ZIKV-infected Ifnar-/- and Ifnar+/- placentas and IFN-beta (IFN-b) or IFN-lambda (IFN-l) treated human mid-gestation chorionic villus explants

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Sex differences during acute myocarditis against coxsackievirus B3 (CVB3)-induced myocarditis (10 dpi) and chronic myocarditis/dilated cardiomyopathy (DCM) against CVB3-induced myocarditis (90 dpi)

Project description:Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that immune responses in the heart are phenotypically distinct in male compared to female mice 10 days after infection resulting in severe DCM in males. Groups consisted of Infected Males, Infected Females, Uninfected Males and Uninfected females. There are 3 mice per group. A total of 12 samples were analyzed in this experiment (12 for 10 dpi and 12 for 90 dpi).

2012-01-19 | E-GEOD-35182 | biostudies-arrayexpress

Sex-Specific DNA Methylation and Gene Expression Changes in Mouse Placentas After Early Preimplantation Alcohol Exposure[RNA-Seq]

Project description:Preimplantation alcohol exposure can negatively impact embryonic development through disruption of molecular profiles and lead to fetal alcohol spectrum disorder (FASD). Despite the central role of the placenta in proper embryonic development and successful pregnancy, studies on the placenta in a FASD context are markedly lacking. Here, preimplantation binge-like alcohol exposure was implemented on pregnant C57BL/6 female mice through subcutaneous injection with two doses of either 2.5 g/kg 50% ethanol or an equivalent volume of saline at 2-h intervals on embryonic day 2.5 corresponding to the 8-cell stage. The placental morphology, DNA methylation and gene expression patterns in male and female late-gestation (E18.5) placentas were assessed. While overall placental morphology was not affected, we found a significant decrease in male ethanol-exposed embryo weights. When looking at molecular profiles, we uncovered numerous differentially methylated regions (DMRs ≥10% difference; 991 in males; 1309 in females) and differentially expressed genes (DEGs; 1046 in males; 340 in females) in the placentas. Remarkably, only 21 DMRs and 54 DEGs were common to both sexes, which were enriched for genes involved in growth factor response pathways. Preimplantation alcohol exposure had a greater impact on imprinted genes expression in male placentas (imprinted DEGs: 18 in males; 1 in females). Finally, by using L1-regularized linear regression, we were able to precisely discriminate control and ethanol-exposed placentas based on their specific DNA methylation patterns. This is the first study demonstrating that preimplantation alcohol exposure alters the DNA methylation and transcriptomic profiles of late-gestation placentas in a sex-specific manner. Importantly, it reveals a placental DNA methylation signature that can detect prenatal alcohol exposure in early life in order to provide appropriate support to attenuate and prevent eventual impact.

2024-02-07 | GSE254846 | GEO

Sex-Specific DNA Methylation and Gene Expression Changes in Mouse Placentas After Early Preimplantation Alcohol Exposure[Methyl-Seq]

2024-02-07 | GSE254845 | GEO

Quantitative Proteomics Analysis of Placenta from Zika Virus Infected Women

Project description:Zika Virus (ZIKV) infection has been associated with fetal abnormalities by compromising placental integrity. Flavivirus have shown deregulation of the host proteome, specially extracellular matrix (ECM) proteins. Our hypothesis is that ZIKV infection of placental tissue deregulates specific ECM proteome, allowing a mechanism of persistent infection and loss of placental integrity. Using nine different placental samples from Puerto Rico collected during 2016 ZIKV epidemic, we compared the proteome of five ZIKV infected samples with uninfected controls. Quantitative proteomics was performed using tandem mass tag TMT10plex™ Isobaric Label Reagent Set followed by Q Exactive™ Hybrid Quadrupole Orbitrap Mass Spectrometry. Identification of proteins was performed by Proteome Discover 2.1, and protein fold change in both groups was compared using Limma software. Differentially expressed proteins were analyzed with STRING and Ingenuity Pathway using both the fold change and p-value. TMT analysis showed that ZIKV infected placentas had 94 reviewed differentially abundant proteins, 32 More abundant and 62 Less abundant. STRING analysis results indicate that 45 of the deregulated proteins are cellular components of the ECM and 16 play a role in its structure and organization. Some of the significantly More abundant proteins were Fibrinogen, Vitronectin and Fibronectin. The results we observed in the samples from naturally infected pregnant women may contribute to the understanding of the mechanism (s) employed by ZIKV during placental infection and give insight on novel targets used to disrupt placental function.

2022-06-09 | PXD023964 | Pride

The study of sex differences during the innate immune response against coxsackievirus B3 (CVB3)-induced myocarditis (12hr post infection)

Project description:Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis. Groups consisted of Infected Males, Infected Females, Uninfected Males and Uninfected females. There are 5 mice per group. A total of 20 samples were analyzed in this experiment.

2011-01-14 | E-GEOD-26630 | biostudies-arrayexpress

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