Hypoxia and oxidative stress induce sterile placental inflammation in vitro

Baker, Barbara S.; Heazell, Alexander E P; Sibley, Colin P.; Wright, Rachael D.; Bischof, Helen; Beards, Frances; Guevara, Tatiana; Girard, Sylvie; Jones, Rebecca L.

doi:10.1038/s41598-021-86268-1

Cited by 36 publications

(35 citation statements)

References 75 publications

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“…This is the same sign of inflammation that is exhibited by hibernating brown bears during torpor [ 48 ], except that in brown bears it is manifested by elevated serum levels of haptoglobin and β-macroglobulin [ 61 ]. Moreover, the levels of IL-1β and TNFα in placental tissues are increased and the relative anti-inflammatory factor IL-10 is reduced after placental hypoxia in humans [ 62 ]; similarly, the present study also found a reduction in IL-10 level during torpor in ground squirrels ( Figure 2 C). There is also evidence indicating that markers of inflammation-related damage are increased in some hibernating tissues during torpor [ 63 , 64 , 65 ], which may be reversible upon arousal [ 39 , 40 ].…”

Section: Discussionsupporting

confidence: 83%

The Protective Effects on Ischemia–Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor–Arousal Cycle of Hibernation

Han

Miao

Hao

et al. 2022

IJMS

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Hibernators are a natural model of vascular ischemia–reperfusion injury; however, the protective mechanisms involved in dealing with such an injury over the torpor–arousal cycle are unclear. The present study aimed to clarify the changes in the thoracic aorta and serum in summer-active (SA), late-torpor (LT) and interbout-arousal (IBA) Daurian ground squirrels (Spermophilus dauricus). The results show that total antioxidant capacity (TAC) was unchanged, but malondialdehyde (MDA), hydrogen peroxide (H2O2), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were significantly increased for the LT group, whereas the levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were significantly reduced in the LT group as compared with the SA group. Moreover, the levels of MDA and IL-1β were significantly reduced, whereas SOD and IL-10 were significantly increased in the IBA group as compared with the SA group. In addition, the lumen area of the thoracic aorta and the expression of the smooth muscle cells (SMCs) contractile marker protein 22α (SM22α) were significantly reduced, whereas the protein expression of the synthetic marker proteins osteopontin (OPN), vimentin (VIM) and proliferating cell nuclear antigen (PCNA) were significantly increased in the LT group as compared with the SA group. Furthermore, the smooth muscle layer of the thoracic aorta was significantly thickened, and PCNA protein expression was significantly reduced in the IBA group as compared with the SA group. The contractile marker proteins SM22α and synthetic marker protein VIM underwent significant localization changes in both LT and IBA groups, with localization of the contractile marker protein α-smooth muscle actin (αSMA) changing only in the IBA group as compared with the SA group. In tunica intima, the serum levels of heparin sulfate (HS) and syndecan-1 (Sy-1) in the LT group were significantly reduced, but the serum level of HS in the IBA group increased significantly as compared with the SA group. Protein expression and localization of endothelial nitric oxide synthase (eNOS) was unchanged in the three groups. In summary, the decrease in reactive oxygen species (ROS) and pro-inflammatory factors and increase in SOD and anti-inflammatory factors during the IBA period induced controlled phenotypic switching of thoracic aortic SMCs and restoration of endothelial permeability to resist ischemic and hypoxic injury during torpor of Daurian ground squirrels.

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Section: Discussionsupporting

confidence: 83%

The Protective Effects on Ischemia–Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor–Arousal Cycle of Hibernation

Han

Miao

Hao

et al. 2022

IJMS

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“…Virtually all placental cell types are sources of oxidative stress, including trophoblasts, endothelial cells in the placenta, Hofbauer macrophages, or stromal cells in the villi [153]. The sustained hypoxia leads to excessive inflammation and oxidative stress, two closely related conditions [154,155]. Furthermore, excessive oxidative stress may lead to a disruption in different placental cells, affecting some critical events, such as apoptosis or autophagy, participating in the pathogenesis of PE [156].…”

Section: Oxidative Stressmentioning

confidence: 99%

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

Ortega

Fraile-Martínez

García-Montero

et al. 2022

Cells

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The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated.

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“…Growing evidence also suggests that endogenous inflammatory mediators such as danger-associated molecular patterns (DAMPs) may contribute to this inflammation and its consequences ( Menon et al, 2016b ; Padron et al, 2020 ). Oxidative stress and hypoxia in the placenta cause the production of several DAMPs, including; uric acid, high mobility group box1 (HMGB1), S100 calcium-binding protein A (S100A), S100 calcium binding protein alpha-12 (S100A12), heat shock protein (HSP) 70 kD, and cell-free fetal DNA (cffDNA) ( Baker et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Fetal DNA Causes Sex-Specific Inflammation From Human Fetal Membranes

Saito-Reis

Kurashima

et al. 2022

Front. Physiol.

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Inflammation is central to the mechanisms of parturition, but the lack of understanding of how it is controlled in normal parturition hampers our ability to understand how it may diverge resulting in preterm birth. Cell-free fetal DNA is found in the amniotic fluid, and it is thought to be able to activate inflammation as a danger-associated molecular pattern. Although its levels increases with gestational age, its effect has not been studied on the human fetal membranes. Thus, the aim of this study was to determine if the fetal DNA can trigger inflammation in the human fetal membranes and, thus, potentially contribute to the inflammatory load. Isolated human amniotic epithelial cells and fetal membrane explants were treated apically with fetal DNA causing the translocation of NF-KB into the nucleus of cells and throughout the cells of the explant layers with time. Fetal membrane explants were treated apically with either small or larger fragments of fetal DNA. IL-6, TNFα, and GM-CSF secretion was measured by ELISA, and pro-MMP2 and pro-MMP9 activity was measured by zymography from apical and basal media. Increased apical IL-6 secretion and basal pro-MMP2 activity was seen with small fragments of fetal DNA. When the data were disaggregated based on fetal sex, males had significant increases in IL-6 secretion and basal increased activity in pro-MMP2 and 9, whereas females had significantly increased basal secretion of TNFα. This was caused by the smaller fragments of fetal DNA, whereas the larger fragments did not cause any significant increases. Male fetal DNA had significantly lower percentages of methylation than females. Thus, when the cytokine and pro-MMP activity data were correlated with methylation percentage, IL-6 secretion significantly correlated negatively, whereas GM-CSF secretion positively correlated. These data support the role of fetal DNA as an inflammatory stimulus in the FM, as measured by increased NF-κB translocation, cytokine secretion, and increased pro-MMP activity. However, the data also suggested that the responses are different from FM tissues of male and female fetuses, and both the fragment size and methylation status of the fetal DNA can influence the magnitude and type of molecule secreted.

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Hypoxia and oxidative stress induce sterile placental inflammation in vitro

Cited by 36 publications

References 75 publications

The Protective Effects on Ischemia–Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor–Arousal Cycle of Hibernation

The Protective Effects on Ischemia–Reperfusion Injury Mechanisms of the Thoracic Aorta in Daurian Ground Squirrels (Spermophilus dauricus) over the Torpor–Arousal Cycle of Hibernation

The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

Fetal DNA Causes Sex-Specific Inflammation From Human Fetal Membranes

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