Effect of spontaneous term labour on the expression of the NR4A receptors nuclear receptor related 1 protein (Nurr1), neuron-derived clone 77 (Nur77) and neuron-derived orphan receptor 1 (NOR1) in human fetal membranes and myometrium

2016 ◽  
Vol 28 (7) ◽  
pp. 893 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Nuclear Receptor ◽  
Muramyl Dipeptide ◽  
Orphan Receptor ◽  
Diaminopimelic Acid ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Membrane Rupture ◽  
Human Labour ◽  
Term Labour ◽  
Bacterial Products

Inflammation has been implicated in the mechanisms responsible for human labour. Emerging evidence indicates that nuclear receptor subfamily 4A (NR4A) receptors regulate the transcription of genes involved in inflammation. The aim of the present study was to determine the effect of spontaneous term labour, Toll-like receptor (TLR) ligands and nucleotide-binding oligomerisation domain-containing (NOD) ligands on the expression of nuclear receptor related 1 protein (Nurr1), neuron-derived clone 77 (Nur77) and neuron-derived orphan receptor 1 (NOR1) in human fetal membranes and myometrium. Human fetal membranes and myometrium were collected from term non-labouring women and women after spontaneous labour onset. Tissue explants were used to determine the effect of the bacterial products lipopolysaccharide (LPS; TLR4 ligand), flagellin (TLR5 ligand), fibroblast-stimulating lipopeptide (FSL-1) (TLR2 ligand), γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) (NOD1 ligand) or minimal peptidoglycan muramyl dipeptide (MDP; NOD2 ligand) on Nurr1, Nur77 and NOR1 expression. Term labour was associated with significantly higher Nurr1 and Nur77, but not NOR1, expression in fetal membranes and myometrium. LPS and MDP increased Nurr1, Nur77 and NOR in fetal membranes; flagellin increased Nurr1 in fetal membranes and the myometrium, as well as NOR1 in the myometrium; and FSL-1 increased Nurr1 expression in fetal membranes. In summary, human labour and bacterial products increase Nurr1, Nur77 and/or NOR1 expression in human fetal membranes and myometrium. This increase in NR4A receptors may contribute to the expression of proinflammatory and pro-labour genes associated with fetal membrane rupture and myometrial contractions.

Labour-associated changes in adrenomedullin content in human placenta and fetal membranes

2003 ◽  
Vol 105 (4) ◽  
pp. 419-423 ◽  
Author(s):  
A. AL-GHAFRA ◽  
N. M. GUDE ◽  
S. P. BRENNECKE ◽  
R. G. KING
Keyword(s):  
Human Placenta ◽  
Mode Of Delivery ◽  
Placental Tissue ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Tissue Extracts ◽  
Human Labour ◽  
Labour Group

The aim of the present study was to determine the effects of labour and mode of delivery on human placental and fetal membrane content of adrenomedullin (AdM). Placentas and fetal membranes were collected either at term or pre-term gestation from women either in labour or not in labour, and AdM was measured in tissue extracts by specific RIA. There were significant increases in AdM concentrations in amnion and choriodecidua for the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM concentration in placental tissue between labour groups. This study provides evidence that fetal membrane AdM is increased in amniotic and choriodecidual tissues in response to labour, and suggests that it may play a role during human labour.

433. Identifying novel biomarkers predictive of impending human labour

2008 ◽  
Vol 20 (9) ◽  
pp. 113
Author(s):  
Y. J. Heng ◽  
M. K. W. Di Quinzio ◽  
M. Permezel ◽  
G. E. Rice ◽  
H. M. Georgiou
Keyword(s):  
Predictive Value ◽  
Interleukin 1 ◽  
Fetal Membranes ◽  
Vaginal Fluid ◽  
Protease Inhibition ◽  
Fatty Acid Binding ◽  
Spontaneous Labour ◽  
Human Labour ◽  
Anti Inflammatory ◽  
Term Labour

Human labour is characterised by structural remodelling of the cervix and overlying fetal membranes, myometrial activation and parturition. We hypothesise that temporal biochemical alterations of the cervix and supracervical fetal membranes associated with impending labour may be reflected in the cervico-vaginal fluid (CVF). 2D PAGE proteomic analysis performed on serial CVF samples collected from women (n = 9) during late pregnancy and in spontaneous labour demonstrated 9 significantly altered protein spots (P < 0.05) in association with term labour. Seven different proteins were identified using electrospray ion-trap mass spectrometry (interleukin-1 receptor antagonist (IL-1ra), cystatin-A, glutathione S-transferase P, peroxiredoxin-2, thioredoxin, Cu,Zn superoxide dismutase, and epidermal fatty-acid binding protein). These proteins are involved in anti-inflammatory activity, protease inhibition, and oxidative stress defence. Validation of these potential biomarkers using ELISA is currently underway. Findings for the anti-inflammatory cytokine, IL-1ra are discussed. CVF was collected weekly from 106 women at 36 weeks' gestation up to and including spontaneous labour. The concentration of IL-1ra was 4-fold lower during labour compared with 15–21 and 22–28 days from labour (P < 0.05) and was also significantly lower (P < 0.05) at 0–7 days compared with 15–21 days before labour. After subdividing the women, the concentration of IL-1ra at 8–14 and 15–21 days before labour was 6-fold lower in women who had prelabour rupture of membranes at term followed by regular contractions compared with women who had spontaneous labour with intact membranes. Receiver-operator characteristic curve analysis indicated that IL-1ra best predicted term labour within 3 days of sampling with a cut-off value of 0.4 m g/mL (sensitivity 50.7%, specificity 72.2%, positive predictive value 36.1%, negative predictive value 82.6%). This IL-1ra validation study suggests that the decrease in IL-1ra in CVF during spontaneous term labour may be associated with proinflammatory-mediated remodelling of the fetal membranes leading to their rupture. (1) Di Quinzio et al. 2008, J. Proteome Res, 7:1916–1921. (2) Heng YJ et al. 2008, Am J Obstet Gynecol, In Press.

scholarly journals Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Human Placenta and Fetal Membranes in Relation to Preterm and Term Labor

2002 ◽  
Vol 87 (3) ◽  
pp. 1353-1361 ◽  
Author(s):  
Ping Xu ◽  
Nadia Alfaidy ◽  
John R. G. Challis
Keyword(s):  
Cervical Ripening ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Trophoblast Cells ◽  
Specific Expression ◽  
Membrane Rupture ◽  
Specific Distribution ◽  
Significant Difference ◽  
Chorion Laeve ◽  
Term Labor

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P &lt; 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P &lt; 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.

scholarly journals TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case.

2021 ◽  
Author(s):  
Corinne Belville ◽  
Flora Ponelle-Chachuat ◽  
Marion Rouzaire ◽  
Christelle Gross ◽  
Bruno Pereira ◽  
...  
Keyword(s):  
Sterile Inflammation ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Premature Rupture ◽  
Membrane Rupture ◽  
Genome Wide ◽  
Fetal Membrane Rupture ◽  
Fine Regulation ◽  
Dual Mechanism

The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon previously exacerbated. Beyond all biological processes implied, inflammation is of primary importance and is qualified as sterile at the end of pregnancy. Complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants taken from the altered (cervix zone) and intact fetal membranes at term and before labor were used in this study. By cross-analyzing genome-wide studies strengthened by in vitro experiments, we deciphered how the expression of Toll-like receptor 4 (TLR4), a well-known actor of pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: 1) the methylation of TLR4 and miRNA promoters and 2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3-UTR of TLR4. Consequently, this study demonstrates that a fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.

Expression of adrenomedullin mRNA is altered with gestation and labour in human placenta and fetal membranes

2006 ◽  
Vol 110 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Alfia Al-Ghafra ◽  
Shaun P. Brennecke ◽  
Roger G. King ◽  
Neil M. Gude
Keyword(s):  
Mrna Expression ◽  
Relative Abundance ◽  
Gestational Age ◽  
Northern Blot Analysis ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Tissue Extracts ◽  
Human Labour ◽  
Positive Correlations ◽  
Labour Group

The aim of the present study was to investigate whether placental and fetal membrane AdM (adrenomedullin) mRNA expression changes with gestation and human labour, as we have previously found labour-associated changes in AdM content in fetal membranes [Al-Ghafra, Gude, Brennecke and King (2003) Clin. Sci. 105, 419–423]. Placentas and fetal membranes were collected either at term or pre-term from women either in-labour or not-in-labour, and AdM mRNA abundance was measured in tissue extracts by Northern blot analysis. Increases were found in the relative abundance of amniotic tissue AdM mRNA in both in-labour and not-in-labour groups at term compared with those at pre-term, and there were positive correlations with gestational age. Relative abundance of choriodecidual tissue AdM mRNA was also significantly elevated in the not-in-labour groups between pre-term and term tissues, although there was no significant correlation with gestational age. However, placental AdM mRNA expression was neither significantly increased at term (compared with pre-term) nor correlated with gestational age. In addition, there were significant increases in AdM mRNA in amnion and choriodecidua in the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM mRNA in placental tissues between labour groups. In conclusion, the present study provides evidence that AdM production by fetal membranes is increased in amniotic and choriodecidual tissues at term, compared with pre-term, and in response to labour.

scholarly journals Prokineticin 1 induces a pro-inflammatory response in murine fetal membranes but does not induce preterm delivery

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 581-591 ◽  
Author(s):  
Tamsin R M Lannagan ◽  
Martin R Wilson ◽  
Fiona Denison ◽  
Jane E Norman ◽  
Rob D Catalano ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mrna Expression ◽  
Preterm Delivery ◽  
Inflammatory Responses ◽  
G Protein Coupled Receptors ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Term Labour ◽  
G Protein Coupled

The mechanisms that regulate the induction of term or preterm delivery (PTD) are not fully understood. Infection is known to play a role in the induction of pro-inflammatory cascades in uteroplacental tissues associated with preterm pathological parturition. Similar but not identical cascades are evident in term labour. In the current study, we used a mouse model to evaluate the role of prokineticins in term and preterm parturition. Prokineticins are multi-functioning secreted proteins that signal through G-protein-coupled receptors to induce gene expression, including genes important in inflammatory responses. Expression of prokineticins (Prok1andProk2) was quantified in murine uteroplacental tissues by QPCR in the days preceding labour (days 16–19).Prok1mRNA expression increased significantly on D18 in fetal membranes (compared with D16) but not in uterus or placenta. Intrauterine injection of PROK1 on D17 induced fetal membrane mRNA expression of the pro-inflammatory mediatorsIl6,Il1b,Tnf,Cxcl2andCxcl5, which are not normally up-regulated until D19 of pregnancy. However, intrauterine injection of PROK1 did not result in PTD. As expected, injection of lipopolysaccharide (LPS) induced PTD, but this was not associated with changes in expression ofProk1or its receptor (Prokr1) in fetal membranes. These results suggest that althoughProk1exhibits dynamic mRNA regulation in fetal membranes preceding labour and induces a pro-inflammatory response when injected into the uterus on D17, it is insufficient to induce PTD. Additionally, prokineticin up-regulation appears not to be part of the LPS-induced inflammatory response in mouse fetal membranes.

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.

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