Effect of influenza A virus infection during pregnancy on the developing fetal brain
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ABSTRACT:
PROVIDER: PRJNA1091030 | ENA |
REPOSITORIES: ENA
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Project description:Epidemiological studies link NDDs with exposure to maternal viral infection in utero. As the immature brain is vulnerable to insult, it is thought that prenatal inflammation alters neurodevelopmental trajectories, leading to NDD pathologies. Using a biologically relevant mouse model of live influenza (flu) infection during pregnancy, we aim to determine if gestational flu infection triggers detrimental maternal cell signaling that leads to NDD-relevant pathologies in offspring. Overall, this work will improve translation to the clinic and will build a foundation for developing targeted therapeutics for NDDs that can be delivered during gestation.
2024-06-20 | GSE262291 | GEO
Project description:Maternal influenza A viral infections in humans are associated with low birth weight, increased risk of pre-term birth, stillbirth and congenital defects. To examine the effect of maternal influenza virus infection on placental and fetal growth, pregnant C57BL/6 mice were inoculated intranasally with influenza A virus A/CA/07/2009 pandemic H1N1 or PBS at E3.5, E7.5 or E12.5, and the placentae and fetuses collecgted and weighed at E18.5. Fetal thymuses were pooled from each litter. Placentae were examined histologically, stained by IHC for CD34 and vascular channels quantified. RNA from E7.5 and E12.5 placentae and E7.5 fetal thymuses was subjected to RNA sequencing and pathway analysis. Placental weights were decreased in litters inoculated with influenza at E3.5 and E7.5. Placentae from E7.5 and E12.5 inoculated litters exhibited decreased labyrinth development and transmembrane protein 150A gene was upregulated in E7.5 placentae. Fetal weights were decreased in litters inoculated at E7.5 and E12.5 compared to controls. RNA sequencing of E7.5 thymuses indicated that 957 genes were downregulated 2-fold including Mal, which is associated with Toll-like receptor signaling and T cell differentiation. There were 28 upregulated genes. It is concluded that maternal influenza A virus infection impairs fetal thymic gene expression as well as restricting placental and fetal growth.
2020-09-11 | GSE157132 | GEO
Project description:Maternal Pregnancy Diet Effect on Fetal Brain Transcriptome
| PRJNA551685 | ENA
Project description:Maternal over- and undernutrition in pregnancy plays a critical role in fetal brain development and function. The effects of different maternal diet compositions on intrauterine programming of the fetal brain in the absence of maternal obesity or maternal undernutrition is a lesser-explored area. The goal of this study was to investigate the impact of two different maternal diets on fetal brain gene expression signatures, fetal/neonatal growth, and neonatal behavior in a mouse model. Female C57Bl/6J mice were fed one of two commercially-available chow diets (pelleted vs. powdered) with differing micronutrient and carbohydrate compositions throughout pregnancy and lactation. The powdered chow diet was richer in carbohydrates and lower in micronutrients than the pelleted chow diet, among other differences. On embryonic day 15.5, embryos were weighed and measured. Fetal brains were snap frozen. RNA was extracted from fetal forebrains for five fetuses per diet group and hybridized to whole genome expression microarrays. Functional analyses identified significant upregulation of canonical pathways and upstream regulators involved in cell cycle regulation, synaptic plasticity, and sensory nervous system development in the fetal brain, and significant downregulation of pathways related to cell and embryo death. Pathways related to DNA damage response, humoral and cell-mediated immune response, carbohydrate and lipid metabolism, small molecule biosynthesis, and amino acid metabolism were also dysregulated. Maternal dietary content is an important variable for researchers evaluating fetal brain development and offspring behavior to consider. Selection of a chow diet matched for micronutrients is crucial to avoid unexpected or undesired effects on offspring brain development and behavior.
2019-12-06 | GSE133525 | GEO
Project description:DNA methylation in developing fetal brain of pig
| PRJNA741788 | ENA
Project description:The normal response to influenza A infection is to remain asymptomatic; indeed, a study of volunteers who tested positive for antibodies against 2009 H1N1 revealed that a majority did not experience symptoms. However, studies of influenza pandemics since the 20th century, and to a lesser degree seasonal flu, suggest that pregnancy increases influenza-associated morbidity and mortality. The confounding effect of pregnancy has been well established to adversely alter the clinical course of influenza, with short term complications to mother and baby apparent, and long-term consequences to the fetus hypothesized. However, how the condition of pregnancy impacts long-term maternal anti-influenza immunity remains contentious; while vaccination studies suggest humoral responses sufficient for protection, published research on adaptive immune responses against influenza formed during pregnancy is limited. This study expands upon published work from our lab and others by comprehensively examining compartmental and systemic changes following pandemic A/California/07/2009 influenza infection. Previously, we linked seasonal influenza infection to clinical observations of adverse outcomes in pregnancy, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we observe that the results of a lower infectious dose of pandemic influenza are similar to that of seasonal influenza. Importantly, we expand upon work which suggests infection during pregnancy may also affect humoral immunity. Our observations of reduced early antibody hemagglutinin inhibition and virus neutralization which resolved within 8 weeks of delivery demonstrate that influenza infection impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This hypothesis is further supported by plasmablast transcriptional data, which demonstrates downregulated B cell metabolism and post-translational modification systems only among pregnant animals. These findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during influenza infection, and propose resolving humoral deficiencies following influenza infection confounded by pregnancy. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.
2020-07-30 | GSE155388 | GEO
Project description:In this study, gene expression was profiled by RNA-seq to examine whole transcriptome of the male and female fetal brain of domesticated pig on the three gestation days 45, 60 and 90. Gene expression in fetal brain was distinct on day 90 compared to days 45 and 60. The homeobox genes were consistently upregulated in the brain of females compared to males during development. The sex of adjacent fetuses influenced gene expression of fetal brain. Extensive exon-level expression changes in the developing brains was observed. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in female brain only whereas receptor mediated signaling pathways were enriched in the male brain alone. Genes that are known markers of neurons and astrocytes were differentially regulated in male and female brain during development. The study further suggests that regulation of ion transportation via placental matrotrophy may play a role in fetal brain development.
2021-09-29 | GSE178970 | GEO
Project description:ZIKV was inoculated (strain FSS13025, Cambodia 2010) subcutaneously at five separate locations on the forearms, each with 107 plaque-forming units (PFU) into a healthy pregnant pigtail macaque at 119 days gestation (~28 weeks human pregnancy) to test directly whether ZIKV causes fetal brain injury.
2016-09-12 | GSE84614 | GEO
Project description:Sex differences in gene expression of developing fetal brain in pig
| PRJNA741772 | ENA
Project description:Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Viral RNA was only rarely detected in the placentas from SARS-CoV-2-positive women in our cohort, with only 1/11 positive for infection at the maternal-fetal interface. Through bulk RNA transcriptomic analyses, we found that placentas from SARS-CoV-2-positive pregnancies exhibited inflammatory markers of immune activation, even in the majority of samples which did not show local invasion of the virus. These markers are associated with pregnancy complications such as preeclampsia and poor fetal outcomes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.
2021-04-14 | GSE171995 | GEO