Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis

Moço, Natália Prearo; Martín, Luiz A. B. San; Pereira, Ana Carolina; Polettini, Jossimara; Peraçoli, José Carlos; Coelho, Kunie Iabuki Rabello; Silva, Márcia Guimarães da

doi:10.1016/j.ejogrb.2013.07.036

Cited by 30 publications

(17 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the major functions of fetal membranes is to protect the fetus during its growth and development in utero. Specifically, the fetal membrane functions to provide mechanical 16,17 and immune protection and acts as a barrier for microbial access 18-20 . This protective role is supported by the biomarkers that are produced by fetal membranes during gestation and parturition 21 .…”

Section: Introductionmentioning

confidence: 99%

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Menon

Richardson

2017

Seminars in Perinatology

202

178

View full text Add to dashboard Cite

Preterm prelabor rupture of the membranes (pPROM) remains a significant obstetric problem that affects 3-4% of all pregnancies and precedes 40% to 50% of all preterm births. pPROM arises from complex, multifaceted pathways. In this review, we summarize some old concepts and introduce some novel theories related to pPROM pathophysiology. Specifically, we introduce the concept that pPROM is a disease of the fetal membranes where inflammation-oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. In addition, we report microfractures in fetal membranes that are likely sites of tissue remodeling during gestation; however, increase in number and morphometry (width and depth) of these microfractures in pPROM membranes suggests reduced remodeling capacity of membranes. Microfractures can act as channels for amniotic fluid leak, and inflammatory cell and microbial migration. Further studies on senescence activation and microfracture formation and their role in maintaining membrane homeostasis are needed to fill the knowledge gaps in our understanding of pPROM as well as provide better screening (biomarker and imaging based) tools for predicting women at high risk for pPROM and subsequent preterm birth.

show abstract

Section: Introductionmentioning

confidence: 99%

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Menon

Richardson

2017

Seminars in Perinatology

202

178

View full text Add to dashboard Cite

show abstract

“…The archetypal receptor in this detection system is TLR4, which is activated by the bacterial cell wall component lipopolysaccharide (LPS). TLR4 is extensively expressed throughout the female reproductive tract including the fetal membranes1718 and placental trophoblasts1920, as well as leukocytes, epithelial and mesenchymal cells in the cervix20 and uterus21. TLR-driven pathways are involved in normal on-time parturition, since mice with null mutation in Tlr4 or Tlr2 exhibit a delay in the timing of term labour2223.…”

mentioning

confidence: 99%

Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth

Chin

Dorian

Hutchinson

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (−)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed E. coli. Local induction by E. coli of inflammatory cytokine genes Il1b, Il6, Tnf and Il10 in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.

show abstract

“…Kim et al [83] showed increased expression of TLR-2 in chorioamniotic membranes with hCAM. Our group provided the first report of increase in TLR-1 and TLR-2 mRNAs in fetal membranes of preterm pregnancies with hCAM, when compared to preterm membranes without hCAM [84]. Kumazaki et al [32] showed that placental macrophages from preterm pregnancies complicated by CAM had increased immunoreactivity to TLR-4, when compared to those without inflammatory infiltrate or term placentas.…”

Section: Tlrs and Nlrs At The Maternal-fetal Interface And Pregnancy mentioning

confidence: 85%

Spontaneous Prematurity, Innate Immune System, and Oxidative Stress at the Maternal-Fetal Interface: An Overview

Moço¹,

Ramos²,

Silva³

et al. 2020

Translational Studies on Inflammation

Self Cite

View full text Add to dashboard Cite

Despite the multifactorial etiology of prematurity, intra-amniotic infection is present in 25-40% of preterm pregnancies. Bacteria in amniotic cavity synthesize phospholipases associated with the production of prostaglandins that leads to rupture of fetal membranes and uterine contractions. Bacterial pathogen-associated molecular patterns (PAMPs) activate pattern recognition receptors (PRRs) such as Toll-like (TLRs) and NOD-like receptors (NLRs), triggering pathways that culminate in the production of cytokines that further increase prostaglandin release. Importantly, endogenous molecules called damage-associated molecular patterns (DAMPs) released under stressful conditions can also activate PRRs. Risk factors for both preterm labor (PTL) and preterm premature rupture of membranes (PPROM), including infection-induced inflammation, may cause an increase of ROS release and depletion of antioxidant defenses. In spite of the similarity between the pathophysiology of PTL and PPROM, there are significant differences regarding molecular mediators, degree of tissue damage, and oxidative stress present in these two conditions. PPROM seems to be a consequence of notable tissue damage resulting from chronic oxidative stress, while PTL is associated with minimal tissue degradation resulting from acute exposure and greater antioxidant status. A better understanding of prematurity pathophysiology and the differences between PTL and PPROM can benefit therapeutic approaches to prevent these important inflammatory syndromes.

show abstract

Gene expression and protein localization of TLR-1, -2, -4 and -6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis

Cited by 30 publications

References 50 publications

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth

Spontaneous Prematurity, Innate Immune System, and Oxidative Stress at the Maternal-Fetal Interface: An Overview

Contact Info

Product

Resources

About