bims-reprim 2020-12-13 papers

Issue of 2020–12–13
six papers selected by
Iva Filipovic, Karolinska Institutet

J Cell Physiol. 2020 Dec 10.

Zika virus infection of first trimester trophoblast cells affects cell migration, metabolism and immune homeostasis control.

Daiana Vota, María Torti, Daniel Paparini, Federico Giovannoni, Fátima Merech, Vanesa Hauk, Guillermina Calo, Rosanna Ramhorst, Cybele Garcia, Claudia Pérez Leirós.

Zika virus (ZIKV) re-emerged after circulating almost undetected for many years and the last spread in 2015 was the major outbreak reported. ZIKV infection was associated with congenital fetal growth anomalies such as microcephaly, brain calcifications, and low birth weight related to fetal growth restriction. In this study, we investigated the effect of ZIKV infection on first trimester trophoblast cell function and metabolism. We also studied the interaction of trophoblast cells with decidual immune populations. Results presented here demonstrate that ZIKV infection triggered a strong antiviral response in first trimester cytotrophoblast-derived cells, impaired cell migration, increased glucose uptake and GLUT3 expression, and reduced brain derived neurotrophic factor (BDNF) expression. ZIKV infection also conditioned trophoblast cells to favor a tolerogenic response since an increased recruitment of CD14+ monocytes bearing an anti-inflammatory profile, increased CD4+ T cells and NK CD56Dim and NK CD56Bright populations and an increment in the population CD4+ FOXP3+ IL-10+ cells was observed. Interestingly, when ZIKV infection of trophoblast cells occurred in the presence of the vasoactive intestinal peptide (VIP) there was lower detection of viral RNA and reduced toll-like receptor-3 and viperin messenger RNA expression, along with reduced CD56Dim cells trafficking to trophoblast conditioned media. The effects of ZIKV infection on trophoblast cell function and immune-trophoblast interaction shown here could contribute to defective placentation and ZIKV persistence at the fetal-maternal interface. The inhibitory effect of VIP on ZIKV infection of trophoblast cells highlights its potential as a candidate molecule to interfere ZIKV infection during early pregnancy.

Keywords: congenital fetal growth anomalies; first trimester trophoblast cells; gestational complications; vasoactive intestinal peptide; zika virus

DOI: https://doi.org/10.1002/jcp.30203

Cell Prolif. 2020 Dec 09. e12967

Single-cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period.

Jingrui Huang, Qi Li, Qiaozhen Peng, Yingming Xie, Weinan Wang, Chenlin Pei, Yanhua Zhao, Rong Liu, Lihui Huang, Tieping Li, Liangqun Xie, Jiejie Zhang, Lei Dai, Jingfei Chen, Jingchi Sun, Weishe Zhang.

OBJECTIVES: The decidua is a tissue that contacts both maternal and foetal components and is pivotal to labour onset due to its location. Due to the heterogeneity of decidual tissue, it is challenging to study its role in the peripartum period. Herein, we analysed the transcriptomes of peripartum decidua at single-cell resolution.
MATERIALS AND METHODS: Single-cell RNA sequencing was performed for 29 231 decidual cells before and after delivery to characterize the transcriptomes.
RESULTS: Eight major cell types (including endothelial cells, fibroblasts) and subtypes of decidual stromal cells, extravillous trophoblasts and T cells were identified and found to have various functions. Compared with before delivery, the activation of decidual stromal cell, extravillous trophoblast and T-cell subtypes to different degrees was observed after delivery. Furthermore, the activation involved multiple functions, such as cell proliferation, and several pathways, such as the activator protein 1 pathway. The results of pseudotemporal ordering showed differentiation of decidual stromal cell and extravillous trophoblast subtypes, suggesting inhomogeneity of these subgroups in decidualization (decidual stromal cell) and invasion (extravillous trophoblast).
CONCLUSIONS: The peripartum decidual tissue is heterogeneous. This study revealed changes in the decidua and its components at single-cell resolution; these findings provide a new perspective for the study of peripartum decidua.

Keywords: decidua; heterogeneity; labour onset; single-cell sequencing; transcriptome

DOI: https://doi.org/10.1111/cpr.12967

JCI Insight. 2020 Dec 10. pii: 143007. [Epub ahead of print]

Identifying a biological signature of prenatal maternal stress.

James M Keane, Ali S Khashan, Fergus P McCarthy, Louise C Kenny, James M Collins, Sarah M O'Donovan, Jillian Rm Brown, John F Cryan, Timothy G Dinan, Gerard Clarke, Siobhain M O'Mahony.

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation which can impact negatively on fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy (n = 104) and IBS cohorts (n = 105) of women at 15- and 20-weeks' gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP) and tumour necrosis factor-α, while anxiety associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine respectively in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions such as IBS.

Keywords: Inflammation; Neuroscience; Obstetrics/gynecology

DOI: https://doi.org/10.1172/jci.insight.143007

Nat Rev Dis Primers. 2020 Dec 10. 6(1): 98

Recurrent pregnancy loss.

Evdokia Dimitriadis, Ellen Menkhorst, Shigeru Saito, William H Kutteh, Jan J Brosens.

Recurrent pregnancy loss is a distressing pregnancy disorder experienced by ~2.5% of women trying to conceive. Recurrent pregnancy loss is defined as the failure of two or more clinically recognized pregnancies before 20-24 weeks of gestation and includes embryonic and fetal losses. The diagnosis of an early pregnancy loss is relatively straightforward, although progress in predicting and preventing recurrent pregnancy loss has been hampered by a lack of standardized definitions, the uncertainties surrounding the pathogenesis and the highly variable clinical presentation. The prognosis for couples with recurrent pregnancy loss is generally good, although the likelihood of a successful pregnancy depends on maternal age and the number of previous losses. Recurrent pregnancy loss can be caused by chromosomal errors, anatomical uterine defects, autoimmune disorders and endometrial dysfunction. Available treatments target the putative risk factors of pregnancy loss, although the effectiveness of many medical interventions is controversial. Regardless of the underlying aetiology, couples require accurate information on their chances of having a baby and appropriate support should be offered to reduce the psychological burden associated with multiple miscarriages. Future research must investigate the pathogenesis of recurrent pregnancy loss and evaluate novel diagnostic tests and treatments in adequately powered clinical trials.

DOI: https://doi.org/10.1038/s41572-020-00228-z

Front Immunol. 2020 ;11 531543

Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease.

Jeffery A Goldstein, Kelly Gallagher, Celeste Beck, Rajesh Kumar, Alison D Gernand.

Events in fetal life impact long-term health outcomes. The placenta is the first organ to form and is the site of juxtaposition between the maternal and fetal circulations. Most diseases of pregnancy are caused by, impact, or are reflected in the placenta. The purpose of this review is to describe the main inflammatory processes in the placenta, discuss their immunology, and relate their short- and long-term disease associations. Acute placental inflammation (API), including maternal and fetal inflammatory responses corresponds to the clinical diagnosis of chorioamnionitis and is associated with respiratory and neurodevelopmental diseases. The chronic placental inflammatory pathologies (CPI), include chronic villitis of unknown etiology, chronic deciduitis, chronic chorionitis, eosinophilic T-cell vasculitis, and chronic histiocytic intervillositis. These diseases are less-well studied, but have complex immunology and show mechanistic impacts on the fetal immune system. Overall, much work remains to be done in describing the long-term impacts of placental inflammation on offspring health.

Keywords: DOHaD; asthma; chorioamnionitis; chronic villitis; maternal-fetal inflammation; neurodevelopmental outcomes; placenta

DOI: https://doi.org/10.3389/fimmu.2020.531543