The role of shed placental DNA in the systemic inflammatory syndrome of preeclampsia

Hartley, James D.R.; Ferguson, Brian J.; Moffett, Ashley

doi:10.1016/j.ajog.2015.03.026

Cited by 33 publications

(29 citation statements)

References 93 publications

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“…In normal pregnancy, fetal DNA is detectable in maternal plasma from 7 weeks of gestation with higher concentration in late pregnancy [83]. Many in vitro experimental studies confirmed fetal DNA as a strong inflammatory agent, which can initiate inflammation through TLR9 activation, release of IL-6, and activation of NF-kB by B cells and mononuclear cells [82,84]. Injection of human fetal but not adult DNA into pregnant mice resulted in fetal resorption with elevated levels of TNF-α and IL-6 and infiltration of inflammatory cells in the placenta [82].…”

Section: Dampsmentioning

confidence: 95%

“…Recent evidence clearly suggests that circulating mtDNA DAMPS cause inflammatory responses via activation of TLR9 signaling pathway [80,81]. Taking a cue from these studies, it can be proposed that poor placentation and trophoblast cell death result in production of mitochondrial milieu containing mtDNA DAMPS which can utilize TLR9 to mount a potent systemic inflammatory response, vascular deficiency, and preeclampsia-like features associated with IUGR [39,82]. In normal pregnancy, fetal DNA is detectable in maternal plasma from 7 weeks of gestation with higher concentration in late pregnancy [83].…”

Section: Dampsmentioning

confidence: 97%

“…Many in vitro experimental studies confirmed fetal DNA as a strong inflammatory agent, which can initiate inflammation through TLR9 activation, release of IL-6, and activation of NF-kB by B cells and mononuclear cells [82,84]. Injection of human fetal but not adult DNA into pregnant mice resulted in fetal resorption with elevated levels of TNF-α and IL-6 and infiltration of inflammatory cells in the placenta [82]. Notably, higher levels of fetal DNA were observed in women with preeclampsia as compared to controls, and this increased level can be even detected 3 weeks before the appearance of symptoms of preeclampsia [79,[82][83][84].…”

Section: Dampsmentioning

confidence: 98%

“…Recent observations clearly suggest that shed nuclear and mitochondrial products can facilitate effector immune responses [78][79][80][81][82][83][84]. It is proposed that cell death and injury can lead to release of nuclear and mitochondrial DNA (mtDNA) which can act as a damage-associated molecular pattern and interact with Toll-like receptor 9 (TLR9) [39].…”

Section: Dampsmentioning

confidence: 99%

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Preeclampsia and health risks later in life: an immunological link

Cheng

Sharma

2016

Semin Immunopathol

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Pregnancy represents a period of physiological stress, and although this stress is experienced for a very modest portion of life, it is now recognized as a window to women's future health, often by unmasking predispositions to conditions that only become symptomatic later in life. In normal pregnancy, the mother experiences mild metabolic syndrome-like condition through week 20 of gestation. A pronounced phenotype of metabolic syndrome may program pregnancy complications such as preeclampsia. Preeclampsia is a serious complication with a myriad of manifestations for mother and offspring. This pregnancy syndrome is a polygenic disease and has been now linked to higher incidence of cardiovascular disease, diabetes, and several other disorders associated with vulnerable organs. Furthermore, the offspring born to preeclamptic mothers also exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases in later life. The etiology of preeclampsia is thought to be primarily associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross-talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Since normal pregnancy is associated with a sequence of events represented by temporal events of inflammation (implantation), anti-inflammation (gestation), and inflammation (parturition), it is quite possible that unscheduled alterations in these regulatory responses may lead to pathologic consequences. Although it is not clear whether immunological alterations occur early in pregnancy, it is proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. This review will focus on important aspects of the immune system that coordinate with placental dysfunction to program preeclampsia and influence health in later life.

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Section: Dampsmentioning

confidence: 95%

Section: Dampsmentioning

confidence: 97%

Section: Dampsmentioning

confidence: 98%

Section: Dampsmentioning

confidence: 99%

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Preeclampsia and health risks later in life: an immunological link

Cheng

Sharma

2016

Semin Immunopathol

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“…Interestingly, women with preeclampsia express higher levels of placental TLR9 (Pineda et al 2011). Self DNA is becoming increasingly considered as a major immunostimulatory molecule responsible for adverse pregnancy outcomes (Hartley et al 2015, Sifakis et al 2015.…”

Section: Cffdnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine

et al. 2020

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Pregnancy complications including preeclampsia, preterm birth, intrauterine growth restriction, and gestational diabetes are the main adverse reproductive outcomes. Excessive inflammation and oxidative stress play crucial roles in the pathogenesis of pregnancy disorders. Curcumin, the main polyphenolic compound derived from Curcuma longa, is mainly known by its anti-inflammatory and antioxidant properties. There are in vitro and in vivo reports revealing the preventive and ameliorating effects of curcumin against pregnancy complications. Here, we aimed to seek mechanisms underlying the modulatory effects of curcumin on dysregulated inflammatory and oxidative responses in various pregnancy complications.

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The role of shed placental DNA in the systemic inflammatory syndrome of preeclampsia

Cited by 33 publications

References 93 publications

Preeclampsia and health risks later in life: an immunological link

Preeclampsia and health risks later in life: an immunological link

Sterile inflammation and pregnancy complications: a review

The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine

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