Prostaglandins and mechanisms of preterm birth

Challis, John; Sloboda, Deborah M.; Alfaidy, Nadia; Lye, S. J.; Gibb, William; Patel, F; Whittle, Wendy; Newnham, John P.

doi:10.1530/rep.0.1240001

Cited by 307 publications

(120 citation statements)

References 32 publications

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“…PG plays a central role in the initiation and progression of labor through their transformation of quiescent uterine tissue into a state of active contractility (4). Studies in human uterine and placental tissues show that inflammatory cytokines, particularly TNF-␣ and IL-1, induce synthesis of PGE 2 and PGI 2 in myometrial cells, amnion cells, and placental trophoblast cells through induction of PG H synthase-2 (4).…”

Section: Discussionmentioning

confidence: 99%

“…Ascending intrauterine colonization, originating as bacterial vaginosis and progressing to infection of the choriodecidua, the fetal membranes, amniotic cavity, and ultimately, the fetus, activates an inflammatory cascade that culminates in preterm birth. Related molecular pathways activated by immunological dysfunction or other stressors likely account for preterm delivery in the 70% of cases where no infectious agent can be identified (4,5). Spontaneous preterm labor is the predominant cause of infant morbidity and mortality and is frequently associated with fetal growth restriction and serious developmental disorders that have lifelong consequences for the child (4,6).…”

mentioning

confidence: 99%

“…The process of normal parturition is associated with elevated gene transcription and accumulation of TNF-␣, IL-6, IL-1, and IL-8 in amniotic fluid and gestational tissues, causing activation of PG synthesis which, in turn, leads to the myometrial contractions that expel the fetus (4,7). In the event of intrauterine infection, inflammatory cytokine expression occurs prematurely despite the antiinflammatory, progesterone-dominated environment (5,7).…”

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confidence: 99%

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Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Robertson

Skinner

Care

2006

The Journal of Immunology

173

139

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IL-10 is highly expressed in the uterus and placenta and is implicated in controlling inflammation-induced pathologies of pregnancy. To investigate the role of IL-10 in regulating preterm labor, the response of IL-10 null mutant mice to low-dose LPS in late gestation was evaluated. When IL-10 null mutant C57BL/6 (IL-10−/−) and control (IL-10+/+) mice were administered LPS on day 17 of pregnancy, the dose of LPS required to elicit 50% preterm fetal loss was 10-fold lower in IL-10−/− mice than in IL-10+/+ mice. Surviving fetuses in IL-10−/− mice exhibited fetal growth restriction at lower doses of LPS than IL-10+/+ mice. Marked elevation of LPS-induced immunoactive TNF-α and IL-6 was evident in the serum, uterus, and placenta of IL-10−/− mice, and TNF-α and IL-6 mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum IL-1α, IFN-γ, and IL-12p40 were increased and soluble TNFRII was diminished in the absence of IL-10, with these changes also reflected in the gestational tissues. Administration of rIL-10 to IL-10−/− mice attenuated proinflammatory cytokine synthesis and alleviated their increased susceptibility to preterm loss. Exogenous IL-10 also protected IL-10+/+ mice from fetal loss. These data show that IL-10 modulates resistance to inflammatory stimuli by down-regulating proinflammatory cytokines in the uterus and placenta. Abundance of endogenous IL-10 in gestational tissues is therefore identified as a critical determinant of resistance to preterm labor, and IL-10 may provide a useful therapeutic agent in this common condition.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Robertson

Skinner

Care

2006

The Journal of Immunology

173

139

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“…The role of AEA at the time of labour is currently unknown, but it may be acting as a reservoir for arachidonic acid, a precursor of prostaglandins, an increase in which is observed in the uterus during labour [26].…”

Section: Comparison Of Plasmamentioning

confidence: 99%

Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma

Lam

Marczylo

El-Talatini

et al. 2008

Analytical Biochemistry

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Running Title: Measurement of anandamide in human plasma Abbreviations: AEA, N-arachidonoylethanolamine (anandamide); AEA-d8, octo-deuterated anandamide; LOD, limit of detection; LOQ, limit of quantification; RSD, relative standard deviation; UPLC, ultra performance liquid chromatography, HPLC, high performance liquid chromatography; MS/MS, tandem mass spectrometry Keywords: anandamide, endocannabinoid, liquid chromatography, mass spectrometry, plasmaThe authors affirm that they have no conflicts of interest.

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“…In some species the fetus clearly plays an important role in the timing of parturition. Specifically, in the pregnant ewe, activation of the fetal hypothalamic -pituitary-adrenal (HPA) axis is critical for the normal onset of labor (McDonald & Nathanielsz 1991, Jacobs et al 1994, Challis et al 2002, Lopez Bernal 2003. Although in humans, activation of the fetal HPA axis does not control the timing of parturition, it appears to play a supportive role in the timing of labor (Lopez Bernal 2003).…”

Section: Introductionmentioning

confidence: 99%

Identification of transcription factors at the site of implantation in the later stages of murine pregnancy

Zhao¹,

Koon²,

Bethin³

2006

Reproduction

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Despite medical advances, preterm delivery continues to complicate 12% of all births in the United States and is a major cause of neonatal deaths. One of the reasons that preterm labor continues to be a significant problem is that very little is understood about the factors involved in normal labor. Many investigators have studied parturition in the mouse and defined essential pathways for normal labor. Prostaglandins play an essential role in mouse labor and are important in human labor as well. We examined the 23 transcription factors from pregnant mouse uterus that change expression after the induction of cyclooxygenase-1, the enzyme that catalyzes the first committed step in prostaglandin synthesis. Using in situ hybridization, we have identified three of these transcription factors, Hoxa10, Hoxa11 and GILZ as being expressed in the decidua and regulated at the end of pregnancy. Both Hoxa10 and Hoxa11 are known to be critical for implantation, but very little is known about their roles in late gestation. GILZ has not previously been identified in the gravid uterus. In summary, we have identified three transcription factors that are regulated in the decidua at the end of pregnancy, suggesting a role in detachment of the fetus and placenta.

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Prostaglandins and mechanisms of preterm birth

Cited by 307 publications

References 32 publications

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice

Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma

Identification of transcription factors at the site of implantation in the later stages of murine pregnancy

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