Transcriptome changes in maternal peripheral blood during term parturition mimic perturbations preceding spontaneous preterm birth

2021 ◽  
Author(s):  
Nardhy Gomez-Lopez ◽  
Roberto Romero ◽  
Jose Galaz ◽  
Gaurav Bhatti ◽  
Bogdan Done ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Peripheral Blood ◽  
Predictive Biomarkers ◽  
Cervical Ripening ◽  
Strongly Correlated ◽  
Uterine Contractility ◽  
Spontaneous Preterm Birth ◽  
Maternal Circulation ◽  
Maternal Peripheral Blood ◽  
Transcriptomic Changes

Abstract The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess labor-specific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth.

scholarly journals Proteomic profiling of human amnion for preterm birth biomarker discovery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maurizio Bruschi ◽  
Martina Bartolucci ◽  
Andrea Petretto ◽  
Francesca Buffelli ◽  
Xhuliana Kajana ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Inflammatory Response ◽  
Biomarker Discovery ◽  
Predictive Biomarkers ◽  
Maternal And Newborn Health ◽  
Spontaneous Preterm Birth ◽  
Bioinformatics Analyses ◽  
Core Proteins ◽  
Matrix Metallopeptidase ◽  
Matrix Metallopeptidase 9

AbstractSpontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

scholarly journals Controversies about the Secondary Prevention of Spontaneous Preterm Birth

2018 ◽  
Vol 78 (06) ◽  
pp. 585-595 ◽  
Author(s):  
Ioannis Kyvernitakis ◽  
Holger Maul ◽  
Franz Bahlmann
Keyword(s):  
Preterm Birth ◽  
Secondary Prevention ◽  
Cervical Ripening ◽  
Transvaginal Sonography ◽  
Spontaneous Preterm Birth ◽  
Long Term Outcome ◽  
Meta Analyses ◽  
Twin Pregnancies ◽  
Singleton Pregnancies

AbstractPreterm birth is one of the major global health problems and part of the Millennium Development goals because of the associated high number of perinatal or neonatal mortality and long-term risks of neurodevelopmental and metabolic diseases. Transvaginal sonography has meanwhile been established as a screening tool for spontaneous preterm birth despite its relatively low sensitivity when considering only the cervical length. Vaginal progesterone has been shown to reduce prematurity rates below 34 weeks in a screening population of singleton pregnancies. Up to now, no positive long-term effect could be demonstrated after 2 years. It seems to have no benefit to prolong pregnancies after a period of preterm contractions and in risk patients without cervical shortening. Meta-analyses still demonstrate conflicting results dependent on quality criteria used for selection. A cerclage is only indicated in singleton pregnancies with previous spontaneous preterm birth and a combined cervical shortening in the current pregnancy. Nevertheless, the short- and long-term outcome has never been evaluated, whereas maternal complications may be increased. There is no evidence for a prophylactic cervical cerclage in twin pregnancies even in cases with cervical shortening. Emergency cerclage remains an indication after individual counseling. The effect of a cervical pessary in singleton pregnancy seems to be more pronounced in studies where a few investigators with increasing experience have treated and followed the patients at risk for preterm birth. Mainly in twin pregnancies, pessary treatment seems to be promising compared to other treatment options of secondary prevention when the therapy is started at early stages of precocious cervical ripening. At present, several international trials with the goal to reduce global rates of prematurity are in progress which will hopefully allow to specify the indications and methods of intervention for certain subgroups. When trials are summarized, prospective meta-analyses carry a lower risk of bias than the meanwhile uncontrolled magnitude of retrospective meta-analyses with conflicting results.

scholarly journals Cell-free fetal DNA and spontaneous preterm birth

Reproduction ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. R137-R145 ◽  
Author(s):  
Sara R van Boeckel ◽  
Donald J Davidson ◽  
Jane E Norman ◽  
Sarah J Stock
Keyword(s):  
Preterm Birth ◽  
Clinical Studies ◽  
Spontaneous Preterm Birth ◽  
Maternal Circulation ◽  
Fetal Dna ◽  
Cell Free Fetal Dna ◽  
Adult Cell ◽  
Adverse Pregnancy ◽  
Sting Pathway ◽  
Preclinical And Clinical Studies

Inflammation is known to play a key role in preterm and term parturition. Cell-free fetal DNA (cff-DNA) is present in the maternal circulation and increases with gestational age and some pregnancy complications (e.g. preterm birth, preeclampsia). Microbial DNA and adult cell-free DNA can be pro-inflammatory through DNA-sensing mechanisms such as Toll-like receptor 9 and the Stimulator of Interferon Genes (STING) pathway. However, the pro-inflammatory properties of cff-DNA, and the possible effects of this on pregnancy and parturition are unknown. Clinical studies have quantified cff-DNA levels in the maternal circulation in women who deliver preterm and women who deliver at term and show an association between preterm labor and higher cff-DNA levels in the 2nd, 3rd trimester and at onset of preterm birth symptoms. Together with potential pro-inflammatory properties of cff-DNA, this rise suggests a potential mechanistic role in the pathogenesis of spontaneous preterm birth. In this review, we discuss the evidence linking cff-DNA to adverse pregnancy outcomes, including preterm birth, obtained from preclinical and clinical studies.

scholarly journals MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0236805
Author(s):  
Edward E. Winger ◽  
Jane L. Reed ◽  
Xuhuai Ji ◽  
Nardhy Gomez-Lopez ◽  
Percy Pacora ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Peripheral Blood ◽  
First Trimester ◽  
Spontaneous Preterm Birth

scholarly journals PARK7 regulates inflammation-induced pro-labour mediators in myometrial and amnion cells

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. 207-218 ◽  
Author(s):  
Ratana Lim ◽  
Gillian Barker ◽  
Martha Lappas
Keyword(s):  
Preterm Birth ◽  
Poly I:C ◽  
Fetal Membranes ◽  
Uterine Contractility ◽  
Spontaneous Preterm Birth ◽  
Induced Expression ◽  
Neonatal Deaths ◽  
Myometrial Cells ◽  
Membrane Rupture ◽  
Term Labour

Preterm birth is a prevalent cause of neonatal deaths worldwide. Inflammation has been implicated in spontaneous preterm birth involved in the processes of uterine contractility and membrane rupture. Parkinson protein 7 (PARK7) has been found to play an inflammatory role in non-gestational tissues. The aims of this study were to determine the expression of PARK7 in myometrium and fetal membranes with respect to term labour onset and to elucidate the effect of PARK7 silencing in primary myometrium and amnion cells on pro-inflammatory and pro-labour mediators. PARK7 mRNA expression was higher in term myometrium and fetal membranes from women in labour compared to non-labouring samples and in amnion from preterm deliveries with chorioamnionitis. In human primary myometrial cells transfected with PARK7 siRNA (siPARK7), there was a significant decrease in IL1B, TNF, fsl-1 and poly(I:C)-induced expression of pro-inflammatory cytokine IL6, chemokines (CXCL8, CCL2), adhesion molecule ICAM1, prostaglandin PGF2α and its receptor PTGFR. Similarly, amnion cells transfected with siPARK7 displayed a decrease in IL1B-induced expression of IL6, CXCL8 and ICAM1. In myometrial cells transfected with siPARK7, there was a significant reduction of NF-κB RELA transcriptional activity when stimulated with fsl-1, flagellin and poly(I:C), but not with IL1B or TNF. Collectively, our novel data describe a role for PARK7 in regulating inflammation-induced pro-inflammatory and pro-labour mediators in human myometrial and amnion cells.

scholarly journals Adiponectin and Omentin Levels as Predictive Biomarkers of Preterm Birth in Patients with Gestational Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Radzisław Mierzyński ◽  
Dominik Dłuski ◽  
Łukasz Nowakowski ◽  
Elżbieta Poniedziałek-Czajkowska ◽  
Bożena Leszczyńska-Gorzelak
Keyword(s):  
Diabetes Mellitus ◽  
Preterm Birth ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Preterm Labor ◽  
Predictive Biomarkers ◽  
Control Group ◽  
Strong Correlations ◽  
Spontaneous Preterm Birth ◽  
Clinical Biomarker

Objective. The aim of this study was to determine any changes in adiponectin and omentin levels in GDM patients who delivered at term and preterm and to evaluate whether adipokines can be useful as a clinical biomarker to predict subsequent preterm delivery. Patients and Methods. The levels of adiponectin and omentin were measured in four groups: (1) women with GDM who delivered at term (n=63); (2) women with GDM who had the symptoms of threatened preterm labor and delivered at term (n=23); (3) women with GDM and spontaneous preterm birth (before 37 completed weeks of gestation) (n=19); (4) women with physiological pregnancy (n=55). Results. In comparison with control group the median adiponectin concentrations were significantly lower in all GDM groups (10737 versus 8879; 7057; 6253 ng/ml, respectively; p<0.01). The median omentin concentrations were also significantly lower in all GDM groups in comparison with control group (469 versus 432; 357; 308 ng/ml, respectively; p<0.01). No significant differences in adiponectin and omentin levels between the GDM, preterm labor, and preterm birth groups were observed. However, there was a trend towards lower adiponectin and omentin levels in preterm birth group. The strong correlations between adiponectin and omentin levels were observed in all groups (R=0.801, p<0.001; R=0.824, p<0.001; R=0.705, p<0.001; R=0.764, respectively; p<0.001). In the univariable logistic regression model, significant correlation between omentin concentrations and preterm birth occurrence was found. Conclusions. Our findings suggest that omentin-1, rather than adiponectin, could be useful as a predictor of preterm birth in patients with gestational diabetes mellitus.

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