Is nitric oxide an essential mediator in cervical inflammation and preterm birth?

Nold, Christopher; Stone, Julie M.; Graham, M.J.; Trinh, Jennifer; Blanchette, Alex; Jensen, Todd

doi:10.1080/14767058.2017.1326898

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…Moreover, we observed that EE exposure reduced the effects of LPS on cervical PGE2 production, thus contributing to the prevention of pathological cervical softening and preterm labor. We also observed an LPS-induced increase of cervical iNOS expression in our model, consistent with previous reports regarding the participation of this pro-inflammatory mediator in preterm birth (Törnblom et al 2005, Nold et al 2018. Similarly to previous reports (Aranda et al 2019), we observed that EE exposure prevented LPS induction of cervical NOS activity in our model.…”

Section: Discussionsupporting

confidence: 93%

The enrichment of maternal environment prevents pre-term birth in a mice model

et al. 2020

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Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented toward reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biologically significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate by 40% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born too soon.

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Section: Discussionsupporting

confidence: 93%

The enrichment of maternal environment prevents pre-term birth in a mice model

et al. 2020

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“…Of importance to note, as previously mentioned, macrophages have the capabilities to produce nitric oxide and prostaglandins. Inhibition of nitric oxide or prostaglandins synthesis suppresses cervix softening and ripening while stimulation of nitric oxide production or prostaglandin treatment advance remodeling and induce preterm birth in rats (125), mice (83,126), and women (127). These findings collectively support the conclusion that nitric oxide and prostaglandins are a critical part of the common mechanism for birth at term and with preterm birth.…”

Section: Schema For Cervix Transformation From Soft To Ripe To Dilatisupporting

confidence: 59%

Immunobiology of Cervix Ripening

Yellon

2020

Front. Immunol.

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The cervix is the essential gatekeeper for birth. Incomplete cervix remodeling contributes to problems with delivery at or post-term while preterm birth is a major factor in perinatal morbidity and mortality in newborns. Lack of cervix biopsies from women during the period preceding term or preterm birth have led to use of rodent models to advanced understanding of the mechanism for prepartum cervix remodeling. The critical transition from a soft cervix to a compliant prepartum lower uterine segment has only recently been recognized to occur in various mammalian species when progesterone in circulation is at or near the peak of pregnancy in preparation for birth. In rodents, characterization of ripening resembles an inflammatory process with a temporal coincidence of decreased density of cell nuclei, decline in cross-linked extracellular collagen, and increased presence of macrophages in the cervix. Although a role for inflammation in parturition and cervix remodeling is not a new concept, a comprehensive examination of literature in this review reveals that many conclusions are drawn from comparisons before and after ripening has occurred, not during the process. The present review focuses on essential phenotypes and functions of resident myeloid and possibly other immune cells to bridge the gap with evidence that specific biomarkers may assess the progress of ripening both at term and with preterm birth. Moreover, use of endpoints to determine the effectiveness of various therapeutic approaches to forestall remodeling and reduce risks for preterm birth, or facilitate ripening to promote parturition will improve the postpartum well-being of mothers and newborns. The maternal immune system in mammals adapts to tolerate the differentiation of novel structures associated with the fetal allograft. Development of two interfaces protect the fetus from rejection and assault by the ecology of the external environment. The internal fetal-maternal interface, as represented by the fetal membranes, placenta, and decidua, is crucial for maintaining maternal inflammatory reactivity for surveillance and responses to pathogens. Discussion of the internal interface is elsewhere and in this special volume (1-3). However, the present review is focused on the external fetal-maternal interface consisting of an amniotic fluid buffer, in a forebag region later in pregnancy as the fetal head engages the lower uterus, and the fetal membranes as they press against the internal os of the cervix. This description of a singleton pregnancy in primates near term applies to rodents, despite anatomical differences in the uterus described below, because observations indicate a single fetal sac engages the internal os of the cervix shortly before labor. The success of this external interface to fend off the biome and virome in the vagina reflects the barrier function of the cervix to protect both the fetus and maternal host structures in the uterus. The cervix barrier function has both immunological and structural components. One part of the mate...

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