Prostaglandins and mechanisms of preterm birth

Challis,

doi:10.1530/reprod/124.1.1

Cited by 70 publications

(111 citation statements)

References 19 publications

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“…Gestation length was extended in the Tlr4-/-females, with mean time of birth 13.2 hours later than in control mice (mean Ϯ SEM ϭ 20.05 Ϯ 0.09 days in Tlr4-/-mice vs 19.50 Ϯ 0.08 days in wild-type mice; P Ͻ .001, Figure 1A). Gestation length was extended in the Tlr4-/-females, with mean time of birth 13.2 hours later than in control mice (mean Ϯ SEM ϭ 20.05 Ϯ 0.09 days in Tlr4-/-mice vs 19.50 Ϯ 0.08 days in wild-type mice; P Ͻ .001, Figure 1A).…”

Section: Tlr4 Deficiency Delays Term Labor and Causes Perinatal Lossmentioning

confidence: 96%

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice

et al. 2015

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An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Because endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesized that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and accelerate the parturition cascade. In pregnant TLR4-deficient (Tlr4-/-) mice, average gestation length was extended by 13 hours and increased perinatal mortality was seen compared with wild-type controls. Quantification of cytokine and uterine activation gene expression showed that late gestation induction of Il1b, Il6, Il12b, and Tnf expression seen in control placenta and fetal membranes was disrupted in Tlr4-/- mice, and accompanied by a transient delay in expression of uterine activation genes, including prostaglandin F receptor, oxytocin receptor, and connexin-43. Leukocyte populations were altered before birth in TLR4-deficient females, with fewer neutrophils and macrophages in the placenta, and fewer dendritic cells and more regulatory T cells in the myometrium. Administration of TLR4 ligand lipopolysaccharide to pregnant wild-type mice induced cytokine expression and fetal loss, whereas Tlr4-/- pregnancies were protected. The small molecule TLR4 antagonist (+)-naloxone increased mean duration of gestation by 16 hours in wild-type mice. Collectively, these data demonstrate that TLR4 is a key upstream regulator of the inflammatory response acting to drive uterine activation and control the timing of labor. Because causal pathways for term and preterm labor converge with TLR4, interventions to manipulate TLR4 signaling may have therapeutic utility for women at risk of preterm labor, or in postterm pregnancy.

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Section: Tlr4 Deficiency Delays Term Labor and Causes Perinatal Lossmentioning

confidence: 96%

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice

et al. 2015

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“…It is involved in the regulation of a wide spectrum of biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. Elevated transcription and accumulation of TNF-α and other cytokines in gestational tissues is proposed to activate prostaglandin synthesis which, in turn, leads to the myometrial contractions 58, 59. Though not present in the Preterm Initiator Gene Set , it is a component of the Term Initiator Gene Set and thus may play a role with normal labor.…”

Section: Commentsmentioning

confidence: 99%

Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor

Weiner

Mason

Dong

et al. 2010

American Journal of Obstetrics and Gynecology

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Objective-Distinct processes govern transition from quiescence to activation during term (TL) and preterm labor (PTL). We sought gene sets responsible for TL and PTL, along with the effector genes necessary for labor independent of gestation and underlying trigger.Methods-Expression was analyzed in term and preterm +/− labor (n =6 subjects/group). Gene sets were generated using logic operations.Results-34 genes were similarly expressed in PTL/TL but absent from nonlabor samples (Effector Set). 49 genes were specific to PTL (Preterm Initiator Set) and 174 to TL (Term Initiator Set). The gene ontogeny processes comprising Term Initiator and Effector Sets were diverse, though inflammation was represented in 4 of the top 10; inflammation dominated the Preterm Initiator Set.Comments-TL and PTL differ dramatically in initiator profiles. Though inflammation is part of the Term Initiator and the Effector Sets, it is an overwhelming part of PTL associated with intraamniotic inflammation.

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“…During late pregnancy, the uterus undergoes a modification under the influence of mechanical signals (uterine stretch) and endocrine or paracrine signals of maternal and fetal origins [2]. The end result is a collective alteration in the uterine smooth muscle or myometrium, termed myometrial activation that is marked at the molecular level by the increased expression of a group of genes encoding contraction-associated proteins (CAPs) such as gap junctions and oxytocin receptors [reviewed in [2,3]]. As a result of myometrial activation, at term the uterine musculature is responsive to uterotonins, spontaneously active, and excitable.…”

Section: Introductionmentioning

confidence: 99%

The focal adhesion protein Hic-5 is highly expressed in the rat myometrium during late pregnancy and labour and co-localizes with FAK

Croke

Pike

MacPhee

2007

Reprod Biol Endocrinol

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Background: Myometrial growth and remodeling of the cytoskeleton and focal adhesions during late pregnancy may be critical aspects of myometrial activation and thus labour. Yet our understanding of these aspects is inhibited by the paucity of information concerning the components of focal adhesions in the myometrium. The focal adhesion protein hydrogen peroxideinducible clone-5 (Hic-5) has recently been found in mononuclear smooth muscle but was not examined in the myometrium during pregnancy. Thus, the goal of this study was to characterize Hic-5 mRNA and protein expression in the rat myometrium during pregnancy and labour.

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Prostaglandins and mechanisms of preterm birth

Cited by 70 publications

References 19 publications

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice

Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor

The focal adhesion protein Hic-5 is highly expressed in the rat myometrium during late pregnancy and labour and co-localizes with FAK

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