Dataset Information

Multi-omics analysis of human placentas from first year of the COVID-19 pandemic reveals sex-dependant effects

ABSTRACT: The COVID-19 pandemic affected millions of pregnant persons, yet the consequences of maternal SARS-CoV-2 infection on the placental function and the fetal health remain poorly characterized. While inflammatory and structural alterations have been described in placentas from exposed pregnancies, the underlying molecular mechanisms are still unclear. The aim of this study was to evaluate transcriptomic alterations in placentas exposed to maternal SARS-CoV-2 infection (COVID+) compared to unexposed placentas (COVID-). We analyzed 67 placentas collected between March 2020 and June 2021 from singleton pregnancies with (n = 41) or without (n = 26) a history of maternal SARS-CoV-2 infection during pregnancy. Demographic, obstetric, placental, and fetal data were extracted from the medical records. SARS-CoV-2 RNA was not detected in any placental sample. Bulk RNA-sequencing was performed on villous biopsies preserved either frozen or in RNALater. Global transcriptomic analysis comparing COVID+ and COVID- placentas revealed an upregulation of genes involved in cytoskeleton organization. Stratified analysis by fetal sex identified a marked sex-specific response, with 43 differentially expressed genes (DEGs) in placenta from female fetuses (XX) in the COVID+ group compared to COVID-, whereas only one DEG was identified in placenta from male fetuses (XY). In XX COVID+ placentas, pathways related to cytoskeleton organization, pregnancy specific processes, and muscle development were altered. These results highlight a sex-specific dysregulation of placental gene expression following maternal SAR-CoV-2 infection, predominantly affecting placentas from female fetuses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE318446 | GEO | 2026/02/05

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.

Project description:Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the worldwide COVID-19 pandemic. While SARS-CoV-2 can infect people of all ages and both sexes, senior populations are at greatest risk of severe disease and worse outcomes, and sexual dimorphism has been reported in COVID-19. COVID-19 causes damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with Covid-19, with many survivors suffering from persistent neurological impairment, potentially accelerating Alzheimer’s disease (AD). This study aims to investigate the mechanisms underlying the impact of age, and sex on neuroinflammation due to SARS-CoV-2 infection using mouse models. Methods: Wild-type C57BL/6 mice were subjected to intranasal inoculation of SARS-CoV-2 lineage B.1.351, followed by daily body weight monitoring. At 7 dpi, viral burden and inflammatory cytokine/chemokine responses in the lung and brain were determined by quantitative RT-PCR, followed by immunohistochemical and transcriptomic analyses. Results: Older age, male sex, showed increased lung viral loads and severity of SARS-CoV-2 infection in mice. No viral RNA was detected in the brains of infected mice; however, IL-6 and CCL2 mRNA increased significantly, particularly in brains of old and APOE4 mice. Unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, and pathway analysis identified innate immunity and defense response to virus and other organisms as the major molecular networks affected in the brain by SARS-CoV-2 infection. Conclusions: Our findings demonstrate that age, and sex, modify the progression and outcome of SARS-CoV-2 infection. SARS-CoV-2 infection triggers neuroinflammatory responses despite the lack of detectable virus in the brain. Changes in molecular networks of innate immunity and defense response to microorganisms underlie the impact of SARS-CoV-2 infection in the brain. These findings in mice mimic epidemiological and clinical observations in humans with Covid-19.

Dataset Information

Multi-omics analysis of human placentas from first year of the COVID-19 pandemic reveals sex-dependant effects

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets