Is myometrial inflammation a cause or a consequence of term human labour?

Singh, Natasha; Herbert, Bronwen R.; Sooranna, Gavin; Orsi, Nicolas M.; Edey, Lydia F; Dasgupta, Tathagata; Sooranna, Suren R.; Yellon, Steven M.; Johnson, Mark R.

doi:10.1530/joe-17-0318

Cited by 38 publications

(34 citation statements)

References 50 publications

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“…Activation and infiltration of immune cells was also not significantly different in the uterus. This trends with current literature indicating leukocyte infiltration of the uterus does not increase until active labor 81,82 . The lack of systemic inflammation (no change in plasma IL-6 and TNF-α irrespective of exosome or PBS injection) indicates that inflammation in the cervix and uterus is highly localized and that signals propagate within this region to exclusively modify the environment to prime specific target tissues for labor.…”

Section: Discussionsupporting

confidence: 89%

Exosomes Cause Preterm Birth in Mice: Evidence for Paracrine Signaling in Pregnancy

Sheller‐Miller

Trivedi

Yellon

et al. 2019

Sci Rep

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Endocrine factors and signals of fetal organ maturation are reported determinants of birth timing. To test the hypothesis that paracrine signaling by exosomes are key regulators of parturition, maternal plasma exosomes from CD-1 mice were isolated and characterized throughout gestation and the biological pathways associated with differentially-expressed cargo proteins were determined. Results indicate that the shape and size of exosomes remained constant throughout gestation; however, a progressive increase in the quantity of exosomes carrying inflammatory mediators was observed from gestation day (E)5 to E19. In addition, the effects of late-gestation (E18) plasma exosomes derived from feto-maternal uterine tissues on parturition was determined. Intraperitoneal injection of E18 exosomes into E15 mice localized in maternal reproductive tract tissues and in intrauterine fetal compartments. Compared to controls that delivered at term, preterm birth occurred in exosome-treated mice on E18 and was preceded by increased inflammatory mediators on E17 in the cervix, uterus, and fetal membranes but not in the placenta. This effect was not observed in mice injected with early-gestation (E9) exosomes. This study provides evidence that exosomes function as paracrine mediators of labor and delivery.

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Section: Discussionsupporting

confidence: 89%

Exosomes Cause Preterm Birth in Mice: Evidence for Paracrine Signaling in Pregnancy

Sheller‐Miller

Trivedi

Yellon

et al. 2019

Sci Rep

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“…Pathophysiologically, it may be initiated by a number of different and overlapping causative factors including intra-amniotic infection, decidual haemorrhage or senescence, cervical weakness, breakdown of maternal–fetal tolerance, declining progesterone activity 1 and sterile inflammation 2 . The culmination of these pathological processes is a process of systemic inflammation, likely similar to the inflammatory pathway associated with early and established term labour (uterine and cervical neutrophil infiltration and release of cytokines, prostaglandins and matrix metalloproteins) 3 – 5 . Thus, increasing attention has been given to the potential use of inflammatory biomarkers to identify women at high risk of subsequent sPTB.…”

Section: Introductionmentioning

confidence: 99%

Cervicovaginal natural antimicrobial expression in pregnancy and association with spontaneous preterm birth

Hezelgrave

Seed

Chin-Smith

et al. 2020

Sci Rep

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, paul t. Seed, evonne c. chin-Smith, Alexandra e. Ridout, Andrew H. Shennan & Rachel M. tribe there is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association between the antimicrobial peptides/proteins elafin and cathelicidin and sPTB. An observational cohort study of 405 women at high-risk, and 214 women at low-risk of sPTB. Protein concentrations of elafin and cathelicidin, and the enzyme human neutrophil elastase (HNE) were measured in over 1,000 cervicovaginal fluid (CVF) samples (10 to 24 weeks' gestation). Adjusted CVF cathelicidin and HNE concentrations (but not elafin) were raised in highrisk women who developed cervical shortening and who delivered prematurely and were predictive of sPTB < 37 weeks, with an area under the curve (AUC) of 0.75 (95% CI 0.68 to 0.81) for cathelicidin concentration at 14 to 15 +6 weeks. Elafin concentrations were affected by gestation, body mass index and smoking. CVF elafin in early pregnancy was modestly predictive of sPTB < 34 weeks (AUC 0.63, 0.56-0.70). Alterations in innate immune response proteins in early pregnancy are predictive of sPTB. further investigation is warranted to understand the drivers for this, and their potential to contribute towards clinically useful prediction techniques. Spontaneous preterm birth (sPTB), defined as spontaneous birth prior to 37 weeks of gestation, is a leading cause of neonatal morbidity and mortality. Pathophysiologically, it may be initiated by a number of different and overlapping causative factors including intra-amniotic infection, decidual haemorrhage or senescence, cervical weakness, breakdown of maternal-fetal tolerance, declining progesterone activity 1 and sterile inflammation 2. The culmination of these pathological processes is a process of systemic inflammation, likely similar to the inflammatory pathway associated with early and established term labour (uterine and cervical neutrophil infiltration and release of cytokines, prostaglandins and matrix metalloproteins) 3-5. Thus, increasing attention has been given to the potential use of inflammatory biomarkers to identify women at high risk of subsequent sPTB. These may have potential to guide prevention and/or management strategies, particularly if measurable in early pregnancy and linked to adverse outcome. Natural antimicrobial peptides/proteins (NAPs), the body's rapid 'first defence' response to foreign antigens, are small cationic host defence molecules functioning within the innate immune system. Expressed throughout the female genital tract at epithelial surfaces, their anti-protease action counteract the effect of protease mediated inflammation and tissue destruction 6. NAPs exhibit antibacterial, antiviral and antifungal activity, largely attributed to disruption of microbial membranes 7. Trappin2/elafin (also known as peptidase inhibitor 3) or skin-derived anti-proteinase (SKALP), secretory...

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“…Another limitation is the preterm samples. In humans, it is extremely difficult to assess nonlaboring preterm samples without additional confounding pathology; a limitation not unique to this study . In the absence of labor, indications for preterm delivery in this study were placenta or vasa praevia, fetal growth restriction, placental abruption, and APH, which are closely related to inflammation .…”

Section: Discussionmentioning

confidence: 92%