Proteomic Profiling Reveals Reprogramming of Maternal-Fetal Immune Responses in Pregnant Women Infected With SARS-CoV-2
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
WeiQi Yao
PROVIDER: PXD036310 | iProX | Fri Aug 26 00:00:00 BST 2022
REPOSITORIES: iProX
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Project description:Pregnant women and their fetuses are particularly susceptible to respiratory pathogens. How they respond to SARS-CoV-2 infection is still under investigation. Here, we studied the transcriptome and phenotype of umbilical cord blood cells in pregnant women infected or not with SARS-CoV-2. We found that symptomatic maternal COVID-19 was associated with a transcriptional erythroid cell signature as compared with asymptomatic and uninfected mothers. We observed an expansion of fetal hematopoietic progenitors skewed towards erythroid differentiation and displaying increased clonogenicity. We found no difference in inflammatory cytokines in the cord blood upon SARS-CoV-2 infection. Interestingly, we showed an activation of hypoxia pathway in cord blood cells from symptomatic COVID-19 mothers, suggesting that maternal hypoxia may be triggering this fetal stress erythropoiesis. Overall, these results show a fetal hematopoietic response to symptomatic COVID-19 in pregnant mothers in the absence of vertically transmitted SARS-CoV-2 infection, which is likely to be a mechanism of fetal adaptation to maternal infection and reduced oxygen supply.
2023-08-10 | GSE224063 | GEO
Project description:During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2 worldwide. The short- and long-term implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. To characterize the fetal immune response to maternal SARS-CoV-2 infection, we performed single-cell RNA sequencing and T cell receptor sequencing on cord blood mononuclear cells from infants born to mothers infected with SARS-CoV-2 in the third trimester. We identified widespread gene expression changes in cord blood leukocytes, including upregulation of interferon-stimulated genes (ISG) and of HLA genes in CD14+ monocytes; decreased activation of CD16+ monocytes; activation of plasmacytoid dendritic cells; and activation and exhaustion of NK cells and T CD8+ cells in the cord blood of infants born to SARS-CoV-2+ mothers. Lastly, we observed fetal TCR repertoire clonal expansion in cord blood T cells from pregnancies complicated by maternal SARS-CoV-2 infection. Our results suggest that even in the absence of vertical transmission, SARS-CoV-2 maternal infection in the third trimester modulates the fetal immune system.
2021-04-06 | GSE165193 | GEO
Project description:Peripheral and cord blood samples from SARS-CoV-2 positive or control pregnant women were profiled using paired-end DNBseq to evaluate transcriptomic changes associated with SARS-CoV-2 infection during pregnancy.
2021-11-11 | GSE185557 | GEO
Project description:The discovery of fetal mRNA transcripts in maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma transcripts common to term pregnant women and their newborns but reduced or absent in the postpartum mothers. In whole blood, 157 potentially-fetal transcripts were identified. RT-PCR confirmed the presence of specific transcripts, SNP analysis confirmed the presence of fetal transcripts in maternal circulation. Comparison of whole blood and plasma samples from the same women suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. [I] We profiled whole antepartum (A), postpartum (P), and umbilical cord (U) blood samples from each of 9 mothers and their 10 newborns (1 set of twins, denoted as a and b after the sample names). [II] We also profiled plasma samples (A, P, and U) from three of those mothers to allow for a direct comparison between blood and plasma.
2014-01-08 | E-GEOD-53669 | biostudies-arrayexpress
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
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. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (∼13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. 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.
2021-04-03 | GSE171381 | GEO
Project description:The discovery of fetal mRNA transcripts in maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma transcripts common to term pregnant women and their newborns but reduced or absent in the postpartum mothers. In whole blood, 157 potentially-fetal transcripts were identified. RT-PCR confirmed the presence of specific transcripts, SNP analysis confirmed the presence of fetal transcripts in maternal circulation. Comparison of whole blood and plasma samples from the same women suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women.
2014-01-08 | GSE53669 | GEO
Project description:Both the fetus and the mother who are involved in maternal anti-fetal rejection during pregnancy show distinct alterations in the peripheral blood transcriptome Total RNA isolated from umbilical cord blood and maternal blood was compared between cases without (Normal) and with maternal anti-fetal rejection (FIRS2) using whole genome DASL assay.
2012-03-31 | E-GEOD-28387 | biostudies-arrayexpress
Project description:Maternal blood, as well as umbilical cord blood samples, were collected and DNA methylation levels were determined by Illumina MethylationEPIC microarray. Methods: Twenty-four subjects were chosen from a previous clinical study. Overweight/obese pregnant women (body mass index ≥24kg/m2) who had an uncomplicated pregnancy at <12+6 weeks of gestation were randomly allocated to either an exercise or a control group. Patients allocated to the exercise group performed 3 exercise bouts per week (at least 30 min/session with a rating of perceived exertion between 12-14) via a cycling program that was initiated within 3 days of randomization until 37 weeks of gestation. Patients allocated to the control group continued their usual daily activities. Maternal blood, as well as umbilical cord blood samples, were collected and DNA methylation levels were determined by Illumina MethylationEPIC microarray.
2024-04-16 | GSE172208 | GEO
Project description:Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2
| PRJNA769665 | ENA