Preeclampsia (PE), the leading cause of maternal and fetal morbidity and mortality, is associated with poor fetal growth, intrauterine growth restriction (IUGR) and low birth weight (LBW). Offspring of women who had PE are at increased risk for cardiovascular (CV) disease later in life. However, the exact etiology of PE is unknown. Moreover, there are no effective interventions to treat PE or alleviate IUGR and the developmental origins of chronic disease in the offspring. The placenta is critical to fetal growth and development. Epigenetic regulatory processes such as histone modifications, microRNAs and DNA methylation play an important role in placental development including contributions to the regulation of trophoblast invasion and remodeling of the spiral arteries. Epigenetic processes that lead to changes in placental gene expression in PE mediate downstream effects that contribute to the development of placenta dysfunction, a critical mediator in the onset of PE, impaired fetal growth and IUGR. Therefore, this review will focus on epigenetic processes that contribute to the pathogenesis of PE and IUGR. Understanding the epigenetic mechanisms that contribute to normal placental development and the initiating events in PE may lead to novel therapeutic targets in PE that improve fetal growth and mitigate increased CV risk in the offspring.

Epigenetic processes during preeclampsia and effects on fetal development and chronic health

In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success. 

Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy.

Pregnancy success requires constant dialogue between the mother and developing conceptus. Such crosstalk is facilitated through complex interactions between maternal and fetal cells at distinct tissue sites, collectively termed the “maternal–fetal interface.” The emergence of single-cell technologies has enabled a deeper understanding of the unique processes taking place at the maternal–fetal interface as well as the discovery of novel pathways and immune and nonimmune cell types. Single-cell approaches have also been applied to decipher the cellular dynamics throughout pregnancy, in parturition, and in obstetrical syndromes such as recurrent spontaneous abortion, preeclampsia, and preterm labor. Furthermore, single-cell technologies have been used during the recent COVID-19 pandemic to evaluate placental viral cell entry and the impact of SARS-CoV-2 infection on maternal and fetal immunity. In this brief review, we summarize the current knowledge of cellular immunobiology in pregnancy and its complications that has been generated through single-cell investigations of the maternal–fetal interface.

Single-Cell Immunobiology of the Maternal–Fetal Interface

During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies (P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50–17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs (P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs (P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC.

/pdf/vitamin-d-deficiency-during-late-pregnancy-mediates-placenta-4eqjmcyq1l.pdf

Vitamin D deficiency during late pregnancy mediates placenta-associated complications.

Preeclampsia (PE), a leading cause of maternal and fetal morbidity and mortality, is closely related to the immune system alterations. However, little is known about the landscape and heterogeneity of maternal immune system at single-cell level among PE patients. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from three early-onset preeclamptic pregnant women and two healthy control, respectively. Single-cell RNA sequencing was performed on 10× genomics platform and single-cell transcriptomes were obtained to characterize immune cell subgroups at the pregnant and postpartum stages. In total, 80,429 single-cell transcriptomes were obtained. 19 cellular compositions were identified, which were categorized into six cell types including T cells, natural killer (NK) cells, B cells, monocytes, plasmacytoid dendritic cells and conventional dendritic cells. There were excessive activation of B cells, monocytes and NK cells in PE patients at the pregnant stage based on comparative analysis. Lower immune response activation was noticed in CD4+ and CD8+ T cells in PE patients, especially the low-activation of memory T cells at the pregnant and postpartum stages. PE patients showed high activation of B cells in pregnancy persisted postpartum and lower activation of memory T cells, indicating their persistent effects on the pathogenesis and recurrence risk of PE. This study provide a broad characterization of the single-cell transcriptome of PBMCs in PE, which contributes to identification of immune imbalance for its monitoring and treatment.

Immune cell profiling of preeclamptic pregnant and postpartum women by single-cell RNA sequencing.

Objectives Pre-eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early- (EOPE) and late-onset of pre-eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. Materials and methods A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre-eclampsia. Single-cell transcriptomics of the maternal-fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. Results We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre-eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre-eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. Conclusion Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre-eclampsia.

Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Yang Hao

Author Tools

Chat about Author

Papers

Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers.