Novel pathways of inflammation in human fetal membranes associated with preterm birth and preterm pre-labor rupture of the membranes

Menon, Ramkumar; Behnia, Faranak; Polettini, Jossimara; Richardson, Lauren

doi:10.1007/s00281-020-00808-x

Cited by 68 publications

(64 citation statements)

References 252 publications

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“…Disruption in the remodeling process may lead to placental under-perfusion once maternal blood flow is established and has been associated with complications and adverse pregnancy outcomes [28]. Furthermore, regulatory mechanisms are needed to balance inflammation to ensure development of the fetus and success of pregnancy [29]. Differences in the distribution, specifically the medians, of a number of cytokines between term and preterm births in the current study may indicate an imbalance in inflammation.…”

Section: Discussionmentioning

confidence: 80%

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Buxton

Meraz‐Cruz

Sánchez

et al. 2021

IJERPH

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Preterm birth (PTB), defined as birth before 37 completed weeks of gestation, is a major cause of infant morbidity and mortality. Inflammation is an important component in the physiopathologic pathway leading to PTB but results from cross-sectional studies on associations between inflammation, as measured by cytokines, and PTB are inconsistent. Timing of cytokine measurement during pregnancy varies between studies and may contribute to inconsistent findings. We investigated the effects of timing on associations between 16 cervico-vaginal cytokines (Eotaxin, IL-10, IL-12p40, IL-17, IL-1RA, sIL-2rα, IL-1a, IL-1β, IL-2, IL-6, IP-10, MCP-1, MIP-1α, MIP-1β, TNFα, and VEGF) and PTB among 90 women throughout pregnancy. We used logistic regression to compare associations between concentrations of cervico-vaginal cytokines from periods in pregnancy and PTB. Trimester 1 cytokines had the strongest positive associations with PTB; for example, OR = 1.76 (95% confidence interval: 1.28, 2.42) for IL-6. Second and third trimester associations were weaker but largely positive. IL-1α was the only cytokine with a negative association (trimesters 2, 3 and overall pregnancy). Strong first trimester associations between cytokines and PTB suggest that measuring cytokines early in pregnancy may hold promise for early identification of PTB risk. Variations in cytokine measurement during pregnancy may contribute to inconsistencies among studies.

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Section: Discussionmentioning

confidence: 80%

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Buxton

Meraz‐Cruz

Sánchez

et al. 2021

IJERPH

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“…APR signaling is associated with inflammatory reactions induced in response to infection or stress (e.g., trauma and tissue injury), and modulates immune responses [ 67 ]. Furthermore, normal term and idiopathic preterm parturitions are closely related to inflammation and immune response [ 68 , 69 ]. Thus, it was natural that APR signaling-related events likely contributed to SPTB in our study population.…”

Section: Discussionmentioning

confidence: 99%

Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation

et al. 2021

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Objective We sought to identify plasma biomarkers associated with spontaneous preterm birth (SPTB, delivery within 21 days of sampling) in women with preterm labor (PTL) without intra-amniotic infection/inflammation (IAI) using label-free quantitative proteomic analysis, as well as to elucidate specific protein pathways involved in these cases. Methods This was a retrospective cohort study comprising 104 singleton pregnant women with PTL (24–32 weeks) who underwent amniocentesis and demonstrated no evidence of IAI. Analysis of pooled plasma samples collected from SPTB cases and term birth (TB) controls (n = 10 for each group) was performed using label-free quantitative mass spectrometry for proteome profiling in a nested case-control study design. Eight candidate proteins of interest were validated by ELISA-based assay and a clot-based assay in the total cohort. Results Ninety-one proteins were differentially expressed (P < 0.05) in plasma samples obtained from SPTB cases, of which 53 (58.2%) were upregulated and 38 (41.8%) were downregulated when compared to TD controls. A validation study confirmed that plasma from women who delivered spontaneously within 21 days of sampling contained significantly higher levels of coagulation factor Ⅴ and lower levels of S100 calcium binding protein A9 (S100A9), especially the former which was independent of baseline variables. The top-ranked pathways related to the 91 differentially expressed proteins were liver-X-receptor/retinoid X receptor (RXR) activation, acute phase response signaling, farnesoid X receptor/RXR activation, coagulation system, and complement system. Conclusions Proteomic analyses in this study identified potential novel biomarkers (i.e., coagulation factor V and S100A9) and potential protein pathways in plasma associated with SPTB in the absence of IAI in women with PTL. The present findings provide novel insights into the molecular pathogenesis and therapeutic targets specific for idiopathic SPTB.

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“…In addition to chemokines and cytokines, bacterial invasion of the amniotic cavity stimulates the production of other inflammatory mediators such as prostaglandins, reactive oxygen radicals, and proteases ( Kallapur et al., 2011 ). These products initiate myometrial contractility, cervical ripening, and induce membrane rupture, together increasing the likelihood of preterm birth ( Menon et al., 2020 ). Intriguingly, as mentioned above, extra-uterine maternal infections, such as pyelonephritis, and pneumonia are also associated with spontaneous preterm birth in the absence of evidence for the hematogenous spread of infection to the maternal-fetal interface.…”

Section: Defining Key Features Of Human Chorioamnionitismentioning

confidence: 99%

Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models

Lutz

Al‐Nasiry

Kramer

et al. 2021

Front. Cell. Infect. Microbiol.

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Inflammation of the chorion and/or amnion during pregnancy is called chorioamnionitis. Acute chorioamnionitis is implicated in approximately 40% of preterm births and has wide-ranging implications for the mother, fetus, and newborn. Large disease burden and lack of therapeutic approaches drive the discovery programs to define and test targets to tackle chorioamnionitis. Central to the advancement of these studies is the use of animal models. These models are necessary to deepen our understanding of basic mechanisms of host-pathogen interactions central to chorioamnionitis disease pathogenesis. Models of chorioamnionitis have been developed in numerous species, including mice, rabbits, sheep, and non-human primates. The various models present an array of strategies for initiating an inflammatory response and unique opportunities for studying its downstream consequences for mother, fetus, or newborn. In this review, we present a discussion of the key features of human chorioamnionitis followed by evaluation of currently available animal models in light of these features and consideration of how these models can be best applied to tackle outstanding questions in the field.

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Novel pathways of inflammation in human fetal membranes associated with preterm birth and preterm pre-labor rupture of the membranes

Cited by 68 publications

References 252 publications

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Timing of Cervico-Vaginal Cytokine Collection during Pregnancy and Preterm Birth: A Comparative Analysis in the PRINCESA Cohort

Proteomic identification of novel plasma biomarkers associated with spontaneous preterm birth in women with preterm labor without infection/inflammation

Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models

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