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Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

ABSTRACT: Objectives:Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. Methods:Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Results:In this study, each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Conclusion:These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

SUBMITTER: Lum FM

PROVIDER: S-EPMC6831931 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

Lum Fok-Moon FM Narang Vipin V Hue Susan S Chen Jie J McGovern Naomi N Rajarethinam Ravisankar R Tan Jeslin Jl JJ Amrun Siti Naqiah SN Chan Yi-Hao YH Lee Cheryl Yp CY Chua Tze-Kwang TK Yee Wearn-Xin WX Yeo Nicholas Kw NK Tan Thiam-Chye TC Liu Xuan X Haldenby Sam S Leo Yee-Sin YS Ginhoux Florent F Chan Jerry Ky JK Hiscox Julian J Chong Chia-Yin CY Ng Lisa Fp LF

Clinical & translational immunology 20191105 11

<h4>Objectives</h4>Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear.<h4>Methods</h4>Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis.<h4>Results</h4>In this study, each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS ...[more]

PMID: 31709049

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Project description:The COVID-19 pandemic has had a significant and enduring influence on global health, including maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above gap, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women immediately after term delivery, seven of which had SARS-CoV-2 infection confirmed by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We separately extracted total RNA from placental tissues from maternal and fetal compartments, constructed cDNA libraries, and sequenced them to assess mRNA. Our analysis revealed 635 differentially expressed genes when a false discovery rate (FDR ≤ 0.05) was applied in the maternal placental tissue, with 518 upregulated and 117 downregulated genes in the SARS-CoV-2-positive women (n = 6) compared with the healthy SARS-CoV-2-negative women (n = 8). In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. We observed a significant downregulation of nine genes belonging to the pregnancy-specific glycoprotein related to the immunoglobulin superfamily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28; FDR ≤ 0.01). Additionally, comparing symptomatic women with healthy women, we identified 1788 DEGs. Furthermore, a signaling pathway enrichment analysis revealed that pathways related to oxidative phosphorylation, insulin secretion, cortisol synthesis, estrogen signaling, oxytocin signaling, antigen processing, and presentation were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risks of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta's anti-viral effects in maternal SARS-CoV-2 infection.

Project description:BackgroundPreeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia.MethodsSurplus chorionic villus sampling (CVS) tissues were collected at 10-12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes.ResultsThirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes.ConclusionsTo our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women approximately 6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher's online edition.

Dataset Information

Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

Publications

Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

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